Dickkopf-related protein 4 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

in the

Dickkopf Dickkopf (DKK) is a family of proteins consisting of five members as of 2020. That is, vertebrates usually contain five genes that are members of the family. The most well-studied is Dickkopf-related protein 1 (DKK1). DKK proteins inhibit the ...

family that in humans is encoded by the ''DKK4''

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 ...

In cats

In 2021, researchers at the

Stanford University School of Medicine The Stanford University School of Medicine is the medical school of Stanford University and is located in Stanford, California, United States. It traces its roots to the Medical Department of the University of the Pacific, founded in San Fra ...

discovered that the gene, located on chromosome B1 of the cat genome, is responsible for patterns on

cats The cat (''Felis catus''), also referred to as the domestic cat or house cat, is a small domesticated carnivorous mammal. It is the only domesticated species of the family Felidae. Advances in archaeology and genetics have shown that the ...

. During embryonic development, the epidermis develops alternating thick and thin (in terms of depth, not width) regions, previously found to match the striped mackerel or blotchy patterns that would be expressed based on mutations in the embryos' ''Transmembrane aminopeptidase Q'' (''Taqpep'') gene. The genes ''DKK4'' and '' Wingless Inhibitory Factor 1'' (''WIF1'') both secrete

Wnt signaling In cellular biology, the Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt, pronounced "wint", is a portmanteau created from the ...

inhibitors, but in cells where both are

upregulated In biochemistry, in the biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell decreases the production and quantities of its cellular components, such as RNA ...

, ''DKK4'' produces much more of its protein than WIF1. In ''DKK4''-positive cells, both Wnt signaling inhibitor and activator genes are upregulated, but inhibitor genes like ''DKK4'' secrete proteins with a larger area of effect. ''DKK4'' expression creates a molecular pre-pattern where the thick epidermal regions will develop, then gradually reduces as the embryo continues to develop. In embryos with the blotchy ''Taqpep'' mutation, ''DKK4'' was expressed less and in a broader pattern compared to embryos with the mackerel pattern version of the gene. ''DKK4'' was also examined in specifically

Abyssinian cats The Abyssinian is a breed of cat with a distinctive "ticked" tabby coat, in which individual hairs are banded with different colours. They are also known simply as Abys. The first members of the breed to be exhibited in England were brought t ...

, which are known for their “ ticked” fur with bands of colors on each hair. Two variants, or

alleles An allele is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule. Alleles can differ at a single position through single nucleotide polymorphisms (SNP), but they can also have insertions and deletions ...

, of ''DKK4'', p.Ala18Val and p.Cys63Tyr, were discovered in cats with obscured tabby markings. In some other

breeds A breed is a specific group of breedable domestic animals having homogeneous appearance (phenotype), homogeneous behavior, and/or other characteristics that distinguish it from other organisms of the same species. In literature, there exist seve ...

and non-breeds of cats, the presence of p.Ala18Val also correlated with the Ticked

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

, while other variants correlated with the Non-Ticked phenotype. These variants caused loss of function of the ''DKK4'' gene and smaller, more tightly packed dark areas.

References

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