Genetically modified animals are animals that have been genetically modified for a variety of purposes including producing drugs, enhancing yields, increasing resistance to disease, etc. The vast majority of genetically modified animals are at the research stage while the number close to entering the market remains small.
Production
The process of genetically engineering mammals is a slow, tedious, and expensive process.Murray, Joo (20) Genetically modified animals . Canada: Brainwaving As with other genetically modified organisms (GMOs), first genetic engineers must isolate the gene they wish to insert into the host organism. This can be taken from a cell containing the gene or artificially synthesised. If the chosen gene or the donor organism's
genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
has been well studied it may already be accessible from a genetic library. The
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
is then combined with other genetic elements, including a promoter and terminator region and usually a
selectable marker
A selectable marker is a gene introduced into cell (biology), cells, especially bacteria or cells in cell culture, culture, which confers one or more traits suitable for artificial selection. They are a type of reporter gene used in laboratory micr ...
DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
is generally inserted into using
microinjection
Microinjection is the use of a glass micropipette to inject a liquid substance at a microscopic or borderline macroscopic level. The target is often a living cell but may also include intercellular space. Microinjection is a simple mechanical pro ...
, where it can be injected through the cell's
nuclear envelope
The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material.
The nuclear envelope consists of two lipid bilayer membran ...
directly into the nucleus, or through the use of viral vectors. The first transgenic animals were produced by injecting viral DNA into embryos and then implanting the embryos in females. It is necessary to ensure that the inserted DNA is present in the
embryonic stem cells
Embryonic stem cells (ESCs) are Cell potency#Pluripotency, pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-Implantation (human embryo), implantation embryo. Human embryos reach the blastocyst stage 4� ...
. The embryo would develop and it would be hoped that some of the genetic material would be incorporated into the reproductive cells. Then researchers would have to wait until the animal reached breeding age and then offspring would be screened for presence of the gene in every cell, using PCR, Southern hybridization, and
DNA sequencing
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, thymine, cytosine, and guanine. The ...
.
New technologies are making genetic modifications easier and more precise.
Gene targeting
Gene targeting is a biotechnological tool used to change the DNA sequence of an organism (hence it is a form of Genome Editing). It is based on the natural DNA-repair mechanism of Homology Directed Repair (HDR), including Homologous Recombinat ...
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
repair systems, have been developed to target insertion to exact locations.
Genome editing
Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly insert ge ...
uses artificially engineered
nuclease
In biochemistry, a nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds that link nucleotides together to form nucleic acids. Nucleases variously affect single and ...
s that create breaks at specific points. There are four families of engineered nucleases: meganucleases,
zinc finger nuclease
Zinc-finger nucleases (ZFNs) are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a nuclease, DNA-cleavage domain. Zinc finger domains can be engineered to target specific desired DNA sequences and this enab ...
s,
transcription activator-like effector nuclease
Transcription activator-like effector nucleases (TALEN) are restriction enzymes that can be engineered to cut specific sequences of DNA. They are made by fusing a TAL effector DNA-binding domain to a DNA cleavage domain (a nuclease which cuts DN ...
s (TALENs), and the Cas9-guideRNA system (adapted from
CRISPR
CRISPR (; acronym of clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. Each sequence within an individual prokaryotic CRISPR is d ...
). TALEN and CRISPR are the two most commonly used and each has its own advantages. TALENs have greater target specificity, while CRISPR is easier to design and more efficient. The development of the CRISPR-Cas9 gene editing system has effectively halved the amount of time needed to develop genetically modified animals.
Humans have
domesticated
Domestication is a multi-generational mutualistic relationship in which an animal species, such as humans or leafcutter ants, takes over control and care of another species, such as sheep or fungi, to obtain from them a steady supply of reso ...
animals since around 12,000 BCE, using
selective breeding
Selective breeding (also called artificial selection) is the process by which humans use animal breeding and plant breeding to selectively develop particular phenotypic traits (characteristics) by choosing which typically animal or plant m ...
or artificial selection (as contrasted with
natural selection
Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the Heredity, heritable traits characteristic of a population over generation ...
). The process of
selective breeding
Selective breeding (also called artificial selection) is the process by which humans use animal breeding and plant breeding to selectively develop particular phenotypic traits (characteristics) by choosing which typically animal or plant m ...
, in which organisms with desired traits (and thus with the desired
genes
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
) are used to breed the next generation and organisms lacking the trait are not bred, is a precursor to the modern concept of genetic modification Various advancements in
genetics
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinians, Augustinian ...
allowed humans to directly alter the
DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
and therefore genes of organisms. In 1972, Paul Berg created the first
recombinant DNA
Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
Rudolf Jaenisch
Rudolf Jaenisch (born on April 22, 1942) is a professor of biology at MIT and a founding member of the Whitehead Institute for Biomedical Research. He is a pioneer of transgenic science, in which an animal’s genetic makeup is altered. Jaenisc ...
embryo
An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...
, making it the world's first transgenic animal. However it took another eight years before transgenic mice were developed that passed the
transgene
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
to their offspring. Genetically modified mice were created in 1984 that carried cloned
oncogenes
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
, predisposing them to developing cancer. Mice with genes knocked out (
knockout mouse
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
) were created in 1989. The first transgenic livestock were produced in 1985 and the first animal to synthesise transgenic proteins in their milk were mice, engineered to produce human tissue
plasminogen
Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is enco ...
activator in 1987.
The first genetically modified animal to be commercialised was the
GloFish
The GloFish is a patented and trademarked brand of fluorescently colored genetically modified fish, genetically modified aquarium fish. They have been created from several different species of fish: zebrafish were the first GloFish available in ...
ultraviolet light
Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of th ...
. It was released to the US market in 2003. The first genetically modified animal to be approved for food use was
AquAdvantage salmon
AquAdvantage salmon is a genetically engineered (GE) fish, a GE Atlantic salmon developed by AquaBounty Technologies in 1989. The typical growth hormone-regulating gene in the Atlantic salmon was replaced with the growth hormone-regulating gen ...
in 2015. The salmon were transformed with a
growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
-regulating gene from a Pacific Chinook salmon and a promoter from an ocean pout enabling it to grow year-round instead of only during spring and summer.
Mammals
GM mammals are created for research purposes, production of industrial or therapeutic products, agricultural uses or improving their health. There is also a market for creating genetically modified pets.Rudinko, Larisa (20). Guidance for industry. USA: Center for veterinary medicin Link. /ref>
Medicine
Mammals are the best
model
A model is an informative representation of an object, person, or system. The term originally denoted the plans of a building in late 16th-century English, and derived via French and Italian ultimately from Latin , .
Models can be divided in ...
s for human disease, making genetic engineered ones vital to the discovery and development of cures and treatments for many serious diseases. Knocking out genes responsible for human genetic disorders allows researchers to study the mechanism of the disease and to test possible cures. Genetically modified mice have been the most common mammals used in
biomedical research
Medical research (or biomedical research), also known as health research, refers to the process of using scientific methods with the aim to produce knowledge about human diseases, the prevention and treatment of illness, and the promotion of ...
, as they are cheap and easy to manipulate. Examples include humanized mice created by
xenotransplantation
Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another.human-animal hybrids for gaining relevant insights in the ''
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...
'' context for understanding of human-specific physiology and pathologies. Pigs are also a good target, because they have a similar body size, anatomical features,
physiology
Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...
, pathophysiological response, and diet. Nonhuman primates are the most similar model organisms to humans, but there is less public acceptance toward using them as research animals. In 2009, scientists announced that they had successfully transferred a gene into a
primate
Primates is an order (biology), order of mammals, which is further divided into the Strepsirrhini, strepsirrhines, which include lemurs, galagos, and Lorisidae, lorisids; and the Haplorhini, haplorhines, which include Tarsiiformes, tarsiers a ...
species (
marmoset
The marmosets (), also known as zaris or sagoin, are twenty-two New World monkey species of the genera '' Callithrix'', '' Cebuella'', '' Callibella'', and ''Mico''. All four genera are part of the biological family Callitrichidae. The term ...
s) and produced a stable line of breeding transgenic primates for the first time. Their first research target for these marmosets was
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
, but they were also considering
amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...
and
Huntington's disease
Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly Genetic disorder#Autosomal dominant, inherited. It typically presents as a triad of progressive psychiatric, cognitive, and ...
.
Human proteins expressed in mammals are more likely to be similar to their natural counterparts than those expressed in plants or microorganisms. Stable expression has been accomplished in sheep, pigs, rats, and other animals. In 2009, the first human biological drug produced from such an animal, a
goat
The goat or domestic goat (''Capra hircus'') is a species of Caprinae, goat-antelope that is mostly kept as livestock. It was domesticated from the wild goat (''C. aegagrus'') of Southwest Asia and Eastern Europe. The goat is a member of the ...
anticoagulant
An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which ...
which reduces the probability of
blood clot
A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulatio ...
s during
surgery
Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...
or
childbirth
Childbirth, also known as labour, parturition and delivery, is the completion of pregnancy, where one or more Fetus, fetuses exits the Womb, internal environment of the mother via vaginal delivery or caesarean section and becomes a newborn to ...
was extracted from the goat's milk. Human alpha-1-antitrypsin is another protein that is used in treating humans with this deficiency. Another area is in creating pigs with greater capacity for human organ transplants (
xenotransplantation
Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another.
Livestock
Livestock are modified with the intention of improving economically important traits such as growth-rate, quality of meat, milk composition, disease resistance and survival. Animals have been engineered to grow faster, be healthier and resist diseases. Modifications have also improved the wool production of sheep and udder health of cows.
Goats have been genetically engineered to produce milk with strong spiderweb-like silk proteins. The goat gene sequence has been modified, using fresh umbilical cords taken from kids, in order to code for the human enzyme
lysozyme
Lysozyme (, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside hydrolase ...
. Researchers wanted to alter the milk produced by the goats, to contain lysozyme in order to fight off bacteria causing
diarrhea
Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
in humans.
Enviropig was a genetically enhanced line of Yorkshire pigs in Canada created with the capability of digesting plant
phosphorus
Phosphorus is a chemical element; it has Chemical symbol, symbol P and atomic number 15. All elemental forms of phosphorus are highly Reactivity (chemistry), reactive and are therefore never found in nature. They can nevertheless be prepared ar ...
more efficiently than conventional Yorkshire pigs.Guelph (2010) Enviropig . Canada: The A
transgene
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
construct consisting of a promoter expressed in the
murine
The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families excep ...
parotid gland
The parotid gland is a major salivary gland in many animals. In humans, the two parotid glands are present on either side of the mouth and in front of both ears. They are the largest of the salivary glands. Each parotid is wrapped around the m ...
and the ''
Escherichia coli
''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
''
phytase
A phytase (''myo''-inositol hexakisphosphate phosphohydrolase) is any type of phosphatase enzyme that catalyzes the hydrolysis of phytic acid (myo-inositol hexakisphosphate) – an indigestible, organic form of phosphorus that is found in many pla ...
gene was introduced into the pig embryo by pronuclear
microinjection
Microinjection is the use of a glass micropipette to inject a liquid substance at a microscopic or borderline macroscopic level. The target is often a living cell but may also include intercellular space. Microinjection is a simple mechanical pro ...
. This caused the pigs to produce the enzyme
phytase
A phytase (''myo''-inositol hexakisphosphate phosphohydrolase) is any type of phosphatase enzyme that catalyzes the hydrolysis of phytic acid (myo-inositol hexakisphosphate) – an indigestible, organic form of phosphorus that is found in many pla ...
, which breaks down the indigestible phosphorus, in their saliva. As a result, they excrete 30 to 70% less phosphorus in manure depending upon the age and diet. The lower concentrations of phosphorus in
surface runoff
Surface runoff (also known as overland flow or terrestrial runoff) is the unconfined flow of water over the ground surface, in contrast to ''channel runoff'' (or ''stream flow''). It occurs when excess rainwater, stormwater, meltwater, or other ...
reduces
algal
Algae ( , ; : alga ) is an informal term for any organisms of a large and diverse group of photosynthetic organisms that are not plants, and includes species from multiple distinct clades. Such organisms range from unicellular microalgae, s ...
growth, because phosphorus is the
limiting nutrient
A limiting factor is a variable of a system that causes a noticeable change in output or another measure of a type of system. The limiting factor is in a pyramid shape of organisms going up from the producers to consumers and so on. A factor not l ...
for algae. Because algae consume large amounts of oxygen, excessive growth can result in dead zones for fish. Funding for the Enviropig program ended in April 2012, and as no new partners were found the pigs were killed. However, the genetic material will be stored at the Canadian Agricultural Genetics Repository Program. In 2006, a pig was engineered to produce
omega-3 fatty acid
Omega−3 fatty acids, also called omega−3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their ...
s through the expression of a roundworm gene.
In 1990, the world's first transgenic
bovine
Bovines (subfamily Bovinae) comprise a diverse group of 10 genera of medium to large-sized ungulates, including Bos, cattle, bison, African buffalo, Bubalus, water buffalos, and the four-horned and spiral-horned antelopes. The members of this gro ...
, Herman the Bull, was developed. Herman was genetically engineered by micro-injected embryonic cells with the human gene coding for
lactoferrin
Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular proteins, globular glycoprotein with a molecular mass of about 80 Atomic mass unit, kDa that is widely repre ...
. The Dutch Parliament changed the law in 1992 to allow Herman to reproduce. Eight calves were born in 1994 and all calves inherited the lactoferrin gene. With subsequent sirings, Herman fathered a total of 83 calves. Dutch law required Herman to be slaughtered at the conclusion of the
experiment
An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs whe ...
. However the Dutch Agriculture Minister at the time, Jozias van Aartsen, granted him a reprieve provided he did not have more offspring after public and scientists rallied to his defence. Together with cloned cows named Holly and Belle, he lived out his retirement at
Naturalis
Naturalis Biodiversity Center () is a national museum of natural history and a research center on biodiversity in Leiden, Netherlands. It was named the European Museum of the Year 2021.
Although its current name and organization are relatively ...
, the National Museum of Natural History in Leiden. On 2 April 2004, Herman was euthanised by
veterinarian
A veterinarian (vet) or veterinary surgeon is a medical professional who practices veterinary medicine. They manage a wide range of health conditions and injuries in non-human animals. Along with this, veterinarians also play a role in animal r ...
s from the
University of Utrecht
Utrecht University (UU; , formerly ''Rijksuniversiteit Utrecht'') is a public research university in Utrecht, Netherlands. Established , it is one of the oldest universities in the Netherlands. In 2023, it had an enrollment of 39,769 students, a ...
because he suffered from
osteoarthritis
Osteoarthritis is a type of degenerative joint disease that results from breakdown of articular cartilage, joint cartilage and underlying bone. A form of arthritis, it is believed to be the fourth leading cause of disability in the world, affect ...
. At the time of his death Herman was one of the oldest bulls in the Netherlands. Herman's hide has been preserved and mounted by
taxidermist
Taxidermy is the art of preserving an animal's body by mounting (over an armature) or stuffing, for the purpose of display or study. Animals are often, but not always, portrayed in a lifelike state. The word ''taxidermy'' describes the process ...
s and is permanently on display in Naturalis. They say that he represents the start of a new era in the way man deals with nature, an icon of scientific progress, and the subsequent public discussion of these issues.
In October 2017, Chinese scientists announced they used
CRISPR gene editing
CRISPR gene editing (; pronounced like "crisper"; an abbreviation for "clustered regularly interspaced short palindromic repeats") is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. ...
technology to create of a line of pigs with better body temperature regulation, resulting in about 24% less body fat than typical livestock.
Researchers have developed GM dairy cattle to grow without horns (sometimes referred to as " polled") which can cause injuries to farmers and other animals. DNA was taken from the genome of Red Angus cattle, which is known to suppress horn growth, and inserted into cells taken from an elite
Holstein
Holstein (; ; ; ; ) is the region between the rivers Elbe and Eider (river), Eider. It is the southern half of Schleswig-Holstein, the northernmost States of Germany, state of Germany.
Holstein once existed as the German County of Holstein (; 8 ...
bull called "Randy". Each of the progeny will be a clone of Randy, but without his horns, and their offspring should also be hornless. In 2011, Chinese scientists generated
dairy cows
Dairy cattle (also called dairy cows) are cattle bred with the ability to produce large quantities of milk, from which dairy products are made. Dairy cattle generally are of the species '' Bos taurus''.
Historically, little distinction was ...
genetically engineered with genes from human beings to produce milk that would be the same as human breast milk. This could potentially benefit mothers who cannot produce breast milk but want their children to have breast milk rather than formula. The researchers claim these transgenic cows to be identical to regular cows. Two months later, scientists from
Argentina
Argentina, officially the Argentine Republic, is a country in the southern half of South America. It covers an area of , making it the List of South American countries by area, second-largest country in South America after Brazil, the fourt ...
presented Rosita, a transgenic cow incorporating two human genes, to produce milk with similar properties as human breast milk. In 2012, researchers from New Zealand also developed a genetically engineered cow that produced allergy-free milk.
In 2016 Jayne Raper and a team announced the first trypanotolerant transgenic cow in the world. This team, spanning the International Livestock Research Institute,
Scotland's Rural College
Scotland's Rural College (SRUC; ) is a Public university#United Kingdom, public land based college, land based Research university, research institution focused on agriculture and life sciences. Its history stretches back to 1899 with the estab ...
, the
Roslin Institute
The Roslin Institute is an animal sciences research institute at Easter Bush, Midlothian, Scotland, part of the University of Edinburgh, and is funded by the Biotechnology and Biological Sciences Research Council.
It is best known for creating ...
's Centre for Tropical Livestock Genetics and Health, and the
City University of New York
The City University of New York (CUNY, pronounced , ) is the Public university, public university system of Education in New York City, New York City. It is the largest urban university system in the United States, comprising 25 campuses: eleven ...
, announced that a Kenyan Boran bull had been born and had already successfully had two children. Tumaini - named for the Swahili word for "hope" - carries a trypanolytic factor from a
baboon
Baboons are primates comprising the biology, genus ''Papio'', one of the 23 genera of Old World monkeys, in the family Cercopithecidae. There are six species of baboon: the hamadryas baboon, the Guinea baboon, the olive baboon, the yellow ba ...
Scientists have genetically engineered several organisms, including some mammals, to include
green fluorescent protein
The green fluorescent protein (GFP) is a protein that exhibits green fluorescence when exposed to light in the blue to ultraviolet range. The label ''GFP'' traditionally refers to the protein first isolated from the jellyfish ''Aequorea victo ...
(GFP), for research purposes. GFP and other similar reporting genes allow easy visualisation and localisation of the products of the genetic modification. Fluorescent pigs have been bred to study human organ transplants, regenerating ocular
photoreceptor cell
A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiation ...
s, and other topics. In 2011 green-fluorescent cats were created to find therapies for
HIV/AIDS
The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
and other diseases as
feline immunodeficiency virus
Feline immunodeficiency virus (FIV) is a lentivirus that affects cats worldwide and 2.5% to 4.4% of felines are infected.
FIV was first isolated in 1986, by Niels C. Pedersen and Janet K. Yamamoto at the UC Davis School of Veterinary Med ...
(FIV) is related to HIV. Researchers from the University of Wyoming have developed a way to incorporate spiders' silk-spinning genes into goats, allowing the researchers to harvest the silk protein from the goats' milk for a variety of applications.
Iberian peninsula
The Iberian Peninsula ( ), also known as Iberia, is a peninsula in south-western Europe. Mostly separated from the rest of the European landmass by the Pyrenees, it includes the territories of peninsular Spain and Continental Portugal, comprisin ...
and to help regulate them in Australia. To protect the Iberian species from viral diseases, the myxoma virus was genetically modified to immunize the rabbits, while in Australia the same myxoma virus was genetically modified to lower fertility in the Australian rabbit population. There have also been suggestions that genetic engineering could be used to bring animals back from extinction. It involves changing the genome of a close living relative to resemble the extinct one and is currently being attempted with the
passenger pigeon
The passenger pigeon or wild pigeon (''Ectopistes migratorius'') is an bird extinction, extinct species of Columbidae, pigeon that was endemic to North America. Its common name is derived from the French word ''passager'', meaning "passing by" ...
. Genes associated with the
woolly mammoth
The woolly mammoth (''Mammuthus primigenius'') is an extinct species of mammoth that lived from the Middle Pleistocene until its extinction in the Holocene epoch. It was one of the last in a line of mammoth species, beginning with the African ...
have been added to the genome of an
African Elephant
African elephants are members of the genus ''Loxodonta'' comprising two living elephant species, the African bush elephant (''L. africana'') and the smaller African forest elephant (''L. cyclotis''). Both are social herbivores with grey skin. ...
, although the lead researcher says he has no intention of using live elephants.
Humans
Gene therapy
Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.
The first attempt at modifying human DNA ...
uses genetically modified viruses to deliver genes which can cure disease in humans. Although gene therapy is still relatively new, it has had some successes. It has been used to treat
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...
s such as
severe combined immunodeficiency
Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in diff ...
and Leber's congenital amaurosis. Treatments are also being developed for a range of other currently incurable diseases, such as
cystic fibrosis
Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
,
sickle cell anemia
Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the oxygen-carrying ...
,
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
,
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
,
diabetes
Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
,
heart disease
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...
, and
muscular dystrophy
Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...
. These treatments only affect
somatic cell
In cellular biology, a somatic cell (), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Somatic cells compose the body of an organism ...
s, which means that any changes would not be inheritable.
Germline
In biology and genetics, the germline is the population of a multicellular organism's cells that develop into germ cells. In other words, they are the cells that form gametes ( eggs and sperm), which can come together to form a zygote. They dif ...
gene therapy results in any change being inheritable, which has raised concerns within the scientific community. In 2015, CRISPR was used to edit the DNA of non-viable human embryos. In November 2018, He Jiankui announced that he had edited the genomes of two human embryos, to attempt to disable the ''
CCR5
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.
In humans, the ''CCR5'' gene that encodes the CCR5 p ...
'' gene, which codes for a receptor that HIV uses to enter cells. He said that twin girls- Lulu and Nana, had been born a few weeks earlier, and that they carried functional copies of CCR5 along with disabled CCR5 ( mosaicism), and were still vulnerable to HIV. The work was widely condemned as unethical, dangerous, and premature.
Fish
Genetically modified fish are used for scientific research, as pets, and as a food source.
Aquaculture
Aquaculture (less commonly spelled aquiculture), also known as aquafarming, is the controlled cultivation ("farming") of aquatic organisms such as fish, crustaceans, mollusks, algae and other organisms of value such as aquatic plants (e.g. Nelu ...
is a growing industry, currently providing over half of the consumed fish worldwide. Through genetic engineering, it is possible to increase growth rates, reduce food intake, remove
allergen
An allergen is an otherwise harmless substance that triggers an allergic reaction in sensitive individuals by stimulating an immune response.
In technical terms, an allergen is an antigen that is capable of stimulating a type-I hypersensitivi ...
ic properties, increase cold tolerance, and provide disease resistance.
Detecting pollution
Fish can also be used to detect aquatic pollution or function as bioreactors. Several groups have been developing
zebrafish
The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...
to detect
pollution
Pollution is the introduction of contaminants into the natural environment that cause harm. Pollution can take the form of any substance (solid, liquid, or gas) or energy (such as radioactivity, heat, sound, or light). Pollutants, the component ...
by attaching fluorescent proteins to genes activated by the presence of pollutants. The fish will then glow and can be used as environmental sensors.
Pets
The
GloFish
The GloFish is a patented and trademarked brand of fluorescently colored genetically modified fish, genetically modified aquarium fish. They have been created from several different species of fish: zebrafish were the first GloFish available in ...
is a brand of genetically modified fluorescent
zebrafish
The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...
with bright red, green, and orange fluorescent color. It was originally developed by one of the groups to detect pollution, but is now part of the ornamental fish trade, becoming the first genetically modified animal to become publicly available as a pet when it was introduced for sale in 2003.
Research
GM fish are widely used in basic research in genetics and development. Two species of fish- zebrafish and
medaka
The Japanese rice fish (''Oryzias latipes''), also known as the medaka, is a member of genus ''Oryzias'' ( ricefish), the only genus in the subfamily Oryziinae. This small (up to about ) native of Japan is a denizen of rice paddies, marshes, po ...
, are most commonly modified, because they have optically clear chorions (membranes in the egg), rapidly develop, and the 1-cell embryo is easy to see and microinject with transgenic DNA. Zebrafish are model organisms for developmental processes, regeneration, genetics, behaviour, disease mechanisms, and toxicity testing. Their transparency allows researchers to observe developmental stages, intestinal functions, and tumour growth. The generation of transgenic protocols (whole organism, cell or tissue specific, tagged with reporter genes) has increased the level of information gained by studying these fish.
Growth
GM fish have been developed with promoters driving an over-production of "all fish"
growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
for use in the
aquaculture
Aquaculture (less commonly spelled aquiculture), also known as aquafarming, is the controlled cultivation ("farming") of aquatic organisms such as fish, crustaceans, mollusks, algae and other organisms of value such as aquatic plants (e.g. Nelu ...
industry, to increase the speed of development and potentially reduce fishing pressure on wild stocks. This has resulted in dramatic growth enhancement in several species, including
salmon
Salmon (; : salmon) are any of several list of commercially important fish species, commercially important species of euryhaline ray-finned fish from the genera ''Salmo'' and ''Oncorhynchus'' of the family (biology), family Salmonidae, native ...
,
trout
Trout (: trout) is a generic common name for numerous species of carnivorous freshwater ray-finned fishes belonging to the genera '' Oncorhynchus'', ''Salmo'' and ''Salvelinus'', all of which are members of the subfamily Salmoninae in the ...
, and tilapia.AquaBounty Technologies have produced a salmon that can mature in half the time as wild salmon. The fish is an Atlantic salmon with a
Chinook salmon
The Chinook salmon (''Oncorhynchus tshawytscha'') is the largest and most valuable species of Oncorhynchus, Pacific salmon. Its common name is derived from the Chinookan peoples. Other vernacular names for the species include king salmon, quinn ...
(''Oncorhynchus tshawytscha'') gene inserted. This allows the fish to produce growth hormones all year round compared to the wild-type fish that produces the hormone for only part of the year. The fish also has a second gene inserted from the eel-like ocean pout that acts like an "on" switch for the hormone. Pout also have
antifreeze protein
Antifreeze proteins (AFPs) or ice structuring proteins refer to a class of polypeptides produced by certain animals, plants, fungi and bacteria that permit their survival in temperatures below the freezing point of water. AFPs bind to small ...
s in their blood, which allow the GM salmon to survive near-freezing waters and continue their development. A wild-type salmon takes 24 to 30 months to reach market size (4–6 kg), whereas the producers of the GM salmon say that it requires only 18 months for the GM fish to reach that size.Environmental Assessment for AquAdvantage Salmon /ref> In November 2015, the FDA of the USA approved the
AquAdvantage salmon
AquAdvantage salmon is a genetically engineered (GE) fish, a GE Atlantic salmon developed by AquaBounty Technologies in 1989. The typical growth hormone-regulating gene in the Atlantic salmon was replaced with the growth hormone-regulating gen ...
for commercial production, sale, and consumption, the first non-plant GMO food to be commercialized.
AquaBounty says that to prevent the genetically modified fish from inadvertently breeding with wild salmon, all of the fish will be female and reproductively sterile, although a small percentage of the females may remain fertile. Some opponents of the GM salmon have dubbed it the "Frankenfish".
Insects
Research
In biological research, transgenic fruit flies (''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
'') are
model organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Mo ...
s used to study the effects of genetic changes on development. Fruit flies are often preferred over other animals due to their short life cycle and low maintenance requirements. It also has a relatively simple genome compared to many
vertebrates
Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain.
The vertebrates make up the subphylum Vertebra ...
, with typically only one copy of each gene, making phenotypic analysis easy. ''Drosophila'' have been used to study genetics and inheritance, embryonic development, learning, behavior, and aging.
Transposons
A transposable element (TE), also transposon, or jumping gene, is a type of mobile genetic element, a nucleic acid sequence in DNA that can change its position within a genome.
The discovery of mobile genetic elements earned Barbara McClinto ...
(particularly P elements) are well developed in ''Drosophila'' and provided an early method to add transgenes to their genome, although this has been taken over by more modern gene-editing techniques.
Population control
Due to their significance to human health, scientists are looking at ways to control mosquitoes through genetic engineering. Malaria-resistant mosquitoes have been developed in the laboratory. by inserting a gene that reduces the development of the malaria parasite and then use
homing endonuclease
The homing endonucleases are a collection of endonucleases encoded either as freestanding genes within introns, as fusions with host proteins, or as self-splicing inteins. They catalyze the hydrolysis of genomic DNA within the cells that synthes ...
s to rapidly spread that gene throughout the male population (known as a gene drive). This has been taken further by swapping it for a lethal gene. In trials the populations of ''
Aedes aegypti
''Aedes aegypti'' ( or from Greek 'hateful' and from Latin, meaning 'of Egypt'), sometimes called the Egyptian mosquito, dengue mosquito or yellow fever mosquito, is a mosquito that spreads diseases like dengue fever, yellow fever, malar ...
'' mosquitoes, the single most important carrier of dengue fever and Zika virus, were reduced by between 80% and by 90%. Another approach is to use the
sterile insect technique
The sterile insect technique (SIT) is a method of biological pest control, biological insect control, whereby overwhelming numbers of infertility, sterile insects are released into the wild. The released insects are preferably male, as this is mo ...
, whereby males genetically engineered to be sterile out compete viable males, to reduce population numbers.
Other
insect
Insects (from Latin ') are Hexapoda, hexapod invertebrates of the class (biology), class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body (Insect morphology#Head, head, ...
pests that make attractive targets are
moth
Moths are a group of insects that includes all members of the order Lepidoptera that are not Butterfly, butterflies. They were previously classified as suborder Heterocera, but the group is Paraphyly, paraphyletic with respect to butterflies (s ...
s. Diamondback moths cause US$4 to $5 billion of damage a year worldwide. The approach is similar to the mosquitoes, where males transformed with a gene that prevents females from reaching maturity will be released. They underwent field trials in 2017. Genetically modified moths have previously been released in field trials. A strain of pink bollworm that were sterilised with radiation were genetically engineered to express a red fluorescent protein making it easier for researchers to monitor them.
Industry
Silkworm, the larvae stage of ''
Bombyx mori
''Bombyx mori'', commonly known as the domestic silk moth, is a moth species belonging to the family Bombycidae. It is the closest relative of '' Bombyx mandarina'', the wild silk moth. Silkworms are the larvae of silk moths. The silkworm is of ...
,'' is an economically important insect in
sericulture
Sericulture, or silk farming, is the cultivation of silkworms to produce silk. Although there are several commercial species of silkworms, the caterpillar of the Bombyx mori, domestic silkmoth is the most widely used and intensively studied silkwo ...
. Scientists are developing strategies to enhance silk quality and quantity. There is also potential to use the silk producing machinery to make other valuable proteins. Proteins expressed by silkworms include;
human serum albumin
Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric.
Albumin ...
monoclonal antibody
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Monoclonal antibodie ...
and N-glycanase. Silkworms have been created that produce
spider silk
Spider silk is a protein fibre or silk spun by spiders. Spiders use silk to make webs or other structures that function as adhesive traps to catch prey, to entangle and restrain prey before biting, to transmit tactile information, or as nest ...
, a stronger but extremely difficult to harvest silk, and even novel silks.
Birds
Attempts to produce genetically modified birds began before 1980. Chickens have been genetically modified for a variety of purposes. This includes studying embryo development, preventing the transmission of bird flu and providing evolutionary insights using
reverse engineering
Reverse engineering (also known as backwards engineering or back engineering) is a process or method through which one attempts to understand through deductive reasoning how a previously made device, process, system, or piece of software accompl ...
to recreate dinosaur-like phenotypes. A GM chicken that produces the drug Kanuma, an enzyme that treats a rare condition, in its egg passed regulatory approval in 2015.
Disease control
One potential use of GM birds could be to reduce the spread of avian disease. Researchers at
Roslin Institute
The Roslin Institute is an animal sciences research institute at Easter Bush, Midlothian, Scotland, part of the University of Edinburgh, and is funded by the Biotechnology and Biological Sciences Research Council.
It is best known for creating ...
have produced a strain of GM chickens (''Gallus gallus domesticus'') that does not transmit avian flu to other birds; however, these birds are still susceptible to contracting it. The genetic modification is an
RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
molecule that prevents the virus reproduction by mimicking the region of the flu virus genome that controls replication. It is referred to as a "decoy" because it diverts the flu virus enzyme, the
polymerase
In biochemistry, a polymerase is an enzyme (Enzyme Commission number, EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by ...
, from functions that are required for virus replication.
Evolutionary insights
A team of geneticists led by
University of Montana
The University of Montana (UM) is a public research university in Missoula, Montana, United States. UM is a flagship institution of the Montana University System and its second largest campus. Fall 2024 saw total enrollment hit 10,811, marki ...
paleontologist Jack Horner is seeking to modify a chicken to express several features present in ancestral
maniraptora
Maniraptora is a clade of coelurosaurian dinosaurs which includes the birds and the non-avian dinosaurs that were more closely related to them than to ''Ornithomimus velox''. It contains the major subgroups Avialae, Dromaeosauridae, Troodontidae, ...
ns but absent in modern birds, such as teeth and a long tail, creating what has been dubbed a 'chickenosaurus'. Parallel projects have produced chicken embryos expressing dinosaur-like skull, leg, and foot anatomy. In 2023, Horner claimed success in creating longer chicken tails, and expressed caution regarding future develompents.
In-ovo sexing
Gene editing is one possible tool in the laying hen breeding industry to provide an alternative to Chick culling. With this technology, breeding hens are given a genetic marker that is only passed down to male offspring. These males can then be identified during incubation and removed from the egg supply, so that only females hatch. For example, the Israeli startup eggXYt uses
CRISPR
CRISPR (; acronym of clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. Each sequence within an individual prokaryotic CRISPR is d ...
to give male eggs a biomarker that makes then glow under certain conditions. Importantly, the resulting laying hen and the eggs it producers are not themselves genetically edited. The European Union's Director General for Health and Food Safety has confirmed that made in this way eggs can be marketed, although none are commercially available as of June 2023.
Amphibians
The first experiments that successfully developed
transgenic
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
amphibians into embryos began in the 1980s with ''Xenopus laevis''. Later, germline transgenic axolotls in Ambystoma mexicanum were produced in 2006 using a technique called I-SceI-mediated transgenesis which utilizes the I-SceI endonuclease
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that can break DNA at specific sites and allow for foreign DNA to be inserted into the genome. Both ''Xenopus laevis'' and Ambystoma mexicanum are model organisms used to study regeneration. In addition, transgenic lines have been produced in other
salamander
Salamanders are a group of amphibians typically characterized by their lizard-like appearance, with slender bodies, blunt snouts, short limbs projecting at right angles to the body, and the presence of a tail in both larvae and adults. All t ...
s including the Japanese newt Pyrrhogaster and Pleurodeles watl. Genetically modified frogs, in particular ''
Xenopus laevis
The African clawed frog (''Xenopus laevis''), also known as simply xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the short black ...
cane toads in Australia
The cane toad in Australia is regarded as an exemplary case of an invasive species. Australia's relative isolation prior to History of Australia (1788–1850), European colonisation and the Industrial Revolution, both of which dramatically in ...
. Many lines of transgenic X. laevis are used to study immunology to address how bacteria and viruses cause infectious disease at the University of Rochester Medical Center's X. laevis Research Resource for Immunobiology (XLRRI). Amphibians can also be used to study and validate regenerative signaling pathways such as the
Wnt pathway
In cellular biology, the Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that Cell signaling, pass signals into a cell through cell surface receptors. The name Wnt, pronounced "wint", is a portmanteau cr ...
. The wound-healing abilities of amphibians have many practical applications and can potentially provide a foundation for scar-free repair in human plastic surgery, such as treating the skin of burn patients.
Amphibians like X. laevis are suitable for experimental
embryology
Embryology (from Ancient Greek, Greek ἔμβρυον, ''embryon'', "the unborn, embryo"; and -λογία, ''-logy, -logia'') is the branch of animal biology that studies the Prenatal development (biology), prenatal development of gametes (sex ...
because they have large embryos that can be easily manipulated and observed during development. In experiments with axolotls, mutants with white pigmented skin are often used because their semi-transparent skin provides an efficient visualization and tracking method for fluorescently tagged proteins like GFP. Amphibians are not always ideal when it comes to the resources required to produce genetically modified animals; along with the one to two-year generation time, ''Xenopus laevis'' can be considered less than ideal for transgenic experiments because of its pseudotetraploid genome. Due to the same genes appearing in the genome multiple times, the chance of
mutagenesis
Mutagenesis () is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using lab ...
experiments working is lower. Current methods of freezing and thawing axolotl sperm render them nonfunctional, meaning transgenic lines must be maintained in a facility and this can get quite costly. Producing transgenic axolotls has many challenges due to their large genome size. Current methods of generating transgenic axolotls are limited to random integration of the transgene cassette into the genome, which can lead to uneven expression or silencing. Gene duplicates also complicate efforts to generate efficient
gene knockout
Gene knockouts (also known as gene deletion or gene inactivation) are a widely used genetic engineering technique that involves the gene targeting, targeted removal or inactivation of a specific gene within an organism's genome. This can be done t ...
s.
Despite the costs, axolotls have unique regenerative abilities and ultimately provide useful information in understanding tissue regeneration because they can regenerate their limbs, spinal cord, skin, heart, lungs, and other organs. Naturally occurring mutant axolotls like the white strain that are often used in research have a transcriptional mutation at the Edn3 gene locus. Unlike other model organisms, the first fluorescently labeled cells in axolotls were differentiated muscle cells instead of embryos. In these initial experiments in the early 2000s, scientists were able to visualize muscle cell regeneration in the axolotl tail using a microinjecting technique, but cells could not be traced for the entire course of regeneration due to too harsh conditions that caused early cell death in labeled cells. Though the process of producing transgenic axolotls was a challenge, scientists were able to label cells for longer durations using a plasmid transfection technique, which involves injecting DNA into cells using an electrical pulse in a process called
electroporation
Electroporation, also known as electropermeabilization, is a microbiological and biotechnological technique in which an electric field is applied to cells to briefly increase the permeability of the cell membrane. The application of a high-vo ...
. Transfecting axolotl cells is thought to be more difficult because of the composition of the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...
(ECM). This technique allows spinal cord cells to be labeled and is very important in studying limb regeneration in many other cells; it has been used to study the role of the immune system in regeneration. Using
gene knockout
Gene knockouts (also known as gene deletion or gene inactivation) are a widely used genetic engineering technique that involves the gene targeting, targeted removal or inactivation of a specific gene within an organism's genome. This can be done t ...
approaches, scientists can target specific regions of DNA using techniques like CRISPR/Cas9 to understand the function of certain genes based on the absence of the gene of interest. For example, gene knockouts of the Sox2 gene confirm this region's role in neural stem cell amplification in the axolotl. The technology to do more complex conditional gene knockouts, or conditional knockouts that give the scientist spatiotemporal control of the gene is not yet suitable for axolotls. However, research in this field continues to develop and is made easier by recent sequencing of the genome and resources created for scientists, including data portals that contain axolotl genome and transcriptome reference assemblies to identify
orthologs
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...
.
Nematodes
The
nematode
The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (h ...
''
Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...
'' is one of the major model organisms for researching
molecular biology
Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
.
RNA interference
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...
(RNAi) was discovered in ''C. elegans'' and could be induced by simply feeding them bacteria modified to express double stranded RNA. It is also relatively easy to produce stable transgenic nematodes and this along with RNAi are the major tools used in studying their genes. The most common use of transgenic nematodes has been studying gene expression and localisation by attaching reporter genes. Transgenes can also be combined with RNAi to rescue phenotypes, altered to study gene function, imaged in real time as the cells develop or used to control expression for different tissues or developmental stages. Transgenic nematodes have been used to study viruses, toxicology, and diseases and to detect environmental pollutants.
Other
Systems have been developed to create transgenic organisms in a wide variety of other animals. The gene responsible for
albinism
Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and reddish pink or blue eyes. Individuals with the condition are referred to as albinos.
Varied use and interpretation of ...
in
sea cucumber
Sea cucumbers are echinoderms from the class (biology), class Holothuroidea ( ). They are benthic marine animals found on the sea floor worldwide, and the number of known holothuroid species worldwide is about 1,786, with the greatest number be ...
s has been found, and used to engineer white sea cucumbers, a rare delicacy. The technology also opens the way to investigate the genes responsible for some of the cucumbers more unusual traits, including
hibernating
Hibernation is a state of minimal activity and metabolic reduction entered by some animal species. Hibernation is a seasonal heterothermy characterized by low body-temperature, slow breathing and heart-rate, and low metabolic rate. It is most ...
in summer, eviscerating their intestines, and dissolving their bodies upon death.
Flatworm
Platyhelminthes (from the Greek language, Greek πλατύ, ''platy'', meaning "flat" and ἕλμινς (root: ἑλμινθ-), ''helminth-'', meaning "worm") is a Phylum (biology), phylum of relatively simple bilaterian, Segmentation (biology), ...
s have the ability to regenerate themselves from a single cell. Until 2017 there was no effective way to transform them, which hampered research. By using microinjection and radiation, scientists have now created the first genetically modified flatworms. The bristle worm, a marine
annelid
The annelids (), also known as the segmented worms, are animals that comprise the phylum Annelida (; ). The phylum contains over 22,000 extant species, including ragworms, earthworms, and leeches. The species exist in and have adapted to vario ...
, has been modified. It is of interest due to its reproductive cycle being synchronized with lunar phases, regeneration capacity and slow evolution rate.
Cnidaria
Cnidaria ( ) is a phylum under kingdom Animalia containing over 11,000 species of aquatic invertebrates found both in fresh water, freshwater and marine environments (predominantly the latter), including jellyfish, hydroid (zoology), hydroids, ...
Nematostella vectensis
The starlet sea anemone (''Nematostella vectensis'') is a species of small sea anemone in the family Edwardsiidae native to the east coast of the United States, with introduced populations along the coast of southeast England and the west coast ...
'' are attractive model organisms to study the
evolution
Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...
of
immunity
Immunity may refer to:
Medicine
* Immunity (medical), resistance of an organism to infection or disease
* ''Immunity'' (journal), a scientific journal published by Cell Press
Biology
* Immune system
Engineering
* Radiofrequence immunity ...
and certain developmental processes. Other organisms that have been genetically modified include
snail
A snail is a shelled gastropod. The name is most often applied to land snails, terrestrial molluscs, terrestrial pulmonate gastropod molluscs. However, the common name ''snail'' is also used for most of the members of the molluscan class Gas ...
s,
gecko
Geckos are small, mostly carnivorous lizards that have a wide distribution, found on every continent except Antarctica. Belonging to the infraorder Gekkota, geckos are found in warm climates. They range from .
Geckos are unique among lizards ...
s,
turtle
Turtles are reptiles of the order (biology), order Testudines, characterized by a special turtle shell, shell developed mainly from their ribs. Modern turtles are divided into two major groups, the Pleurodira (side necked turtles) and Crypt ...
s,
crayfish
Crayfish are freshwater crustaceans belonging to the infraorder Astacidea, which also contains lobsters. Taxonomically, they are members of the superfamilies Astacoidea and Parastacoidea. They breathe through feather-like gills. Some spe ...
,
oyster
Oyster is the common name for a number of different families of salt-water bivalve molluscs that live in marine or brackish habitats. In some species, the valves are highly calcified, and many are somewhat irregular in shape. Many, but no ...
s,
shrimp
A shrimp (: shrimp (American English, US) or shrimps (British English, UK)) is a crustacean with an elongated body and a primarily Aquatic locomotion, swimming mode of locomotion – typically Decapods belonging to the Caridea or Dendrobranchi ...
,
clam
Clam is a common name for several kinds of bivalve mollusc. The word is often applied only to those that are deemed edible and live as infauna, spending most of their lives halfway buried in the sand of the sea floor or riverbeds. Clams h ...
s,
abalone
Abalone ( or ; via Spanish , from Rumsen language, Rumsen ''aulón'') is a common name for any small to very large marine life, marine gastropod mollusc in the family (biology), family Haliotidae, which once contained six genera but now cont ...
, and
sponge
Sponges or sea sponges are primarily marine invertebrates of the animal phylum Porifera (; meaning 'pore bearer'), a basal clade and a sister taxon of the diploblasts. They are sessile filter feeders that are bound to the seabed, and a ...
s.
Food products derived from genetically modified (GM) animals have not yet entered the European market. Nonetheless, the on-going discussion about GM crops and the developing debate about the safety and ethics of foods and pharmaceutical products produced by both GM animals and plants, have provoked varying views across different sectors of society
Ethics
Genetic modification
Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including th ...
and
genome editing
Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly insert ge ...
hold potential for the future, but decisions regarding the use of these technologies must be based not only on what is possible, but also on what is ethically reasonable. Principles such as animal integrity, naturalness, risk identification and animal welfare are examples of ethically important factors that must be taken into consideration, and they also influence public perception and regulatory decisions by authorities.
The utility of extrapolating animal data to humans has been questioned. This has led ethical committees to adopt the principles of the four Rs (Reduction, Refinement, Replacement, and Responsibility) as a guide for decision-making regarding animal experimentation. However, complete abandonment of laboratory animals has not yet been possible, and further research is needed to develop a roadmap for robust alternatives before their use can be fully discontinued.