Canine Pigment Type Switch

Some breeds like Golden Retrievers and Labrador Retrievers or varieties like white Poodles or black German Shepherds produce only one type of pigment and have a single-colored coat.

But most dogs can produce both eumelanin and phaeomelanin and have banded hairs, hair banding or hair tipping, or other patterns with areas of both darker and lighter pigment.

Here you can learn what makes a pigment cell switch from one pigment type to the other and how the E Locus, K Locus and A Locus interact to create different patterns.

But: This information is a bit technical and is helpful but in no way essential for grasping the concept of canine color inheritance. Feel free to skip this chapter or come back later.

Content

The E Locus

Melanocytes are melanin-producing pigment cells found in the hair follicle.

These cells produce phaeomelanin by default, unless they are told otherwise.

Phaeomelanin is a yellow-red pigment. But varying pigment density can produce different shades from off-white to yellow or even dark red.

Eumelanin is a black pigment, but can be modified to brown, blue, or lilac. Pigment cells can produce eumelanin but they need an external signal to actually do so.

Pigment Type Switch Dogs single colored coat

But how can the pigment cells be told what pigment type to make?

That’s where the E-Locus comes into play!

The extension locus or short E locus encodes the building plan for a receptor found in the membrane of melanocytes. This Melanocortin 1 Receptor or MC1R can be activated from outside of the cell. If the right molecule binds to MC1R the pigment cell gets a signal to activate eumelanin production.

If all things work according to plan this switch from phaeomelanin to eumelanin happens when α-Melanocyte-stimulating hormone (α-MSH) is secreted by the pituitary gland and binds to MC1R.

Pigment Type Switch Dogs Extension Locus

Pigment Type Switch Dogs Extension Locus alpha MSH

The various alleles on the E-Locus are building plans for some slightly different versions of the melanocortin 1 receptor:

E^m is the dominant allele in this series. It produces a melanistic mask on top of any pattern.
E is the wild-type allele and just enables normal pattern expression.
e^G, e^A, e^H are reduced-function alleles that cause a domino phenotype with bigger and lighter phaeomelanin markings and a reduced ability to produce eumelanin. Domino alleles can be described as partial recessive red since they reduce (but not fully remove) the functionality of MC1R.
e is a loss-of-funtion mutant that basically deactivates MC1R^[2]. This causes a solid recessive red phenotype in all pigmented areas. Homozygous e/e dogs can not build a functional receptor. The pigment cells consequently remain locked in their default setting to only produce phaeomelanin.

Pigment Type Switch Dogs Extension Locus ee loss of function

The A Locus

The agouti locus or short A locus holds the building plan for agouti signalling protein or ASIP.

ASIP wants to bind to the melanocortin 1 receptor, it functions as a competitive antagonist to α-MSH and blocks access to MC1R. So if ASIP is present α-MSH can’t bind to MC1R and can’t signal the cell to produce eumelanin. And without a signal from α-MSH the melanocytes produce phaeomelanin.

ASIP expression in different body parts increases phaeomelanin synthesis.

ASIP expression is controlled by two promoter regions.

The hair cycle promoter (HCP) regulates ASIP expression on the upper body.

The wild type HCP2 is expressed in intervals. this causes dorsal hair banding with alternating stripes of eumelanin and phaeomelanin. The more active HCP1 variant causes predominantly yellow hairs, some with darker tips (sabling). The less active HCP3,4,5 give predominantly black hairs, some with pale roots.

The ventral promoter (HCP) regulates ASIP expression on the lower body.

This promoter controls the extension of ventral tan markings. The wild type VP2 gives classic tan points. The more active VP1 extends these tan markings unto the upper body.

The different alleles of the A locus represent promoter haplotypes and cause different basic patterns:

A^y or clear sable (VP1-HCP1) gives a predominantly yellow coat with minimal sabling.
A^ys or shaded sable (VP2-HCP1) gives a predominantly yellow coat with more sabling.
a^w or agouti (VP2-HCP2) gives dorsal hair banding and wild type tan points.
a^sa or saddle (VP1-HCP3,4,5) gives extended tan markings and limits black hairs to the saddle.
a^t or tan point (VP2-HCP3,4,5) gives a predominantly black coat with wild type tan points.
a is a loss-of-funtion mutation that disables ASIP. It causes recessive black since α-MSH now regains the competitive advantage and can bind to MC1R and activate the production of eumelanin.

Pigment Type Switch Dogs Agouti Locus Recessive Black aa

The K Locus

The DEFB103 gene at the K locus encodes the building plan for β-Defensin 103 (CBD103). This protein normally is part of the innate immune response system of the skin.

In dogs, there is a mutated version of the β-Defensin 103 known as the K^B allele.

The K^B gene product binds to MC1R where it promotes eumelanin production. it blocks both ASIP and α-MSH from binding to MC1R^[1].

There are three gene variants at the K locus:

K^B is the dominant allele in this series and causes dominant black. K^B masks the A locus pattern.
k^br causes a brindle pattern with eumelanic stripes on top of the pattern.
k^y is the wild type and does not interfere with coat colors.

A ghost tan phenotype enables A locus pattern bleed-through in K^B dogs.

Summary

A quick overview on how genes interact in different combinations:

E	K	A	Phenotype
E^m/-	K^B/-	–	Dominant Black + Mask
E^m/-	k^br/-	A^y/-	Sable + Mask + Brindle
E^m/-	k^br/-	A^ys/-	Shaded Sable + Mask + Brindle
E^m/-	k^br/-	a^w/-	Agouti + Mask + Brindle
E^m/-	k^br/-	a^t/-	Tan Point + Mask + Brindle
E^m/-	k^br/-	a^sa/-	Saddle Pattern + Mask + Brindle
E^m/-	k^br/-	a/a	Recessive Black + Mask
E^m/-	k^y/k^y	A^y/-	Sable + Mask
E^m/-	k^y/k^y	A^ys/-	Shaded Sable + Mask
E^m/-	k^y/k^y	a^w/-	Agouti + Mask
E^m/-	k^y/k^y	a^t/-	Tan Point + Mask
E^m/-	k^y/k^y	a^sa/-	Saddle Pattern + Mask
E^m/-	k^y/k^y	a/a	Recessive Black + Mask
E/-	K^B/-	–	Dominant Black
E/-	k^br/-	A^y/-	Sable + Brindle
E/-	k^br/-	A^ys/-	Shaded Sable + Brindle
E/-	k^br/-	a^w/-	Agouti + Brindle
E/-	k^br/-	a^t/-	Brindlepoint
E/-	k^br/-	a^sa/-	Saddle Pattern + Brindle
E/-	k^br/-	a/a	Recessive Black
E/-	k^y/k^y	A^y/-	Sable
E/-	k^y/k^y	A^ys/-	Shaded Sable
E/-	k^y/k^y	a^w/-	Agouti
E/-	k^y/k^y	a^t/-	Tan Point
E/-	k^y/k^y	a^sa/-	Saddle Pattern
E/-	k^y/k^y	a/a	Recessive Black
e^A/- e^G/- e^H/-	K^B/- k^br/- k^y/k^y	A^y/- A^ys/- a^w/- a^sa/- a^t/- a/a	Various Domino Phenotypes
e/e	–	–	Recessive Red

Learn More

Links

[1] Candille SI, Kaelin CB, Cattanach BM, Yu B, Thompson DA, et al. (2007) A beta-defensin mutation causes black coat color in domestic dogs. Science 11(1): 24–30. https://doi.org/10.1126/science.1147880

[2] Newton, J., Wilkie, A., He, L. et al. Melanocortin 1 receptor variation in the domestic dog. Incorporating Mouse Genome 11, 24–30 (2000). https://doi.org/10.1007/s003350010005

[3] Honkanen, L., Loechel, R., Davison, S., Donner, J., & Anderson, H. (2024). Canine coat color E locus updates: Identification of a new MC1R variant causing’sable’coat color in English Cocker Spaniels and a proposed update to the E locus dominance hierarchy. Animal Genetics. https://doi.org/10.1111/age.13398