Canine Pigment Type Switch

Some dogs produce only eumelanin (black pigment) in their coat. Others produce only phaeomelanin (red pigment). But many dogs produce a bit of both pigments.

There is a wide range of possibilities for pigment distribution in the coat.

Learn what makes a pigment cell switch from one type of pigment to the other and how the E Locus, K Locus, and A Locus interact to create all the different base patterns in dogs.

Pigment Types

The melanocytes are melanin-producing pigment cells.

These “pigment factories” can produce either eumelanin or phaeomelanin.

Phaeomelanin is a red pigment. But red intensity can vary from off-white to red.

Eumelanin is a black pigment. But it can be modified to brown, blue, or lilac.

Pigment cells in the hair follicle produce phaeomelanin by default. Unless they are told otherwise.

In order to produce eumelanin, the pigment cells need a signal from outside the cell.

The E Locus

The extension locus (E locus) encodes the building plan for the Melanocortin 1 Receptor (MC1R).

This receptor is located in the membrane of pigment cells.

The MC1R can be activated externally if the right molecule binds to the MC1R. This activates the receptor so that the pigment cells switch from their default pheomelanin to eumelanin synthesis.

The pituitary gland and skin spontaneously secrete α-Melanocyte-stimulating hormone (α-MSH).

The α-MSH binds to MC1R and gives a signal to switch from phaeomelanin to eumelanin.

This gives us the baseline situation for the E locus:

  • The pigment cells want to make phaeomelanin.
  • But they get a permanent signal from α-MSH via MC1R (E locus) to make eumelanin.

The alleles of the E locus each build a slightly different version of the melanocortin 1 receptor.

The order of dominance goes from more eumelanin to less eumelanin:

  • Em is the dominant allele in this series. It produces a melanistic mask on top of any base pattern.
  • E is the wild-type allele and just enables normal base pattern expression via the A locus and K locus.
  • eG, eA, and eH 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.

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 does this so effectively that it blocks the access of α-MSH to the MC1R.

If ASIP is present, α-MSH cannot bind to MC1R, and the affected cells produce phaeomelanin.

Pigment Type Switch Dogs Agouti Locus

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 onto the upper body.

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

The order of dominance goes from more phaeomelanin to less phaeomelanin:

  • Ay or clear sable (VP1-HCP1) gives a predominantly yellow coat with minimal sabling.
  • Ays or shaded sable (VP2-HCP1) gives a predominantly yellow coat with more sabling.
  • aw or agouti (VP2-HCP2) gives dorsal hair banding and wild type tan points.
  • asa or saddle (VP1-HCP3,4,5) gives extended tan markings and limits black hairs to the saddle.
  • at 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.
coatsandcolors.com Pigment Type Switch Dogs ASIP loss of function recessive black 1

The K Locus

The DEFB103 gene at the K locus encodes the building plan for β-Defensin 103 (CBD103).

This protein is normally 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 KB allele.

The KB gene product binds to MC1R where it promotes eumelanin production.

KB blocks both ASIP and α-MSH from binding to MC1R[1].

coatsandcolors.com Pigment Type Switch Dogs dominant black KB activates eumelanin synthesis 1

There are three gene variants at the K locus.

The order of dominance goes from more eumelanin to less eumelanin:

  • KB is the dominant allele in this series and causes dominant black. KB masks the A locus pattern.
  • kbr causes a brindle pattern with eumelanic stripes on top of the pattern.
  • ky is the wild type and does not interfere with coat colors.

A ghost tan phenotype enables A locus pattern bleed-through in some KB dogs.

Summary

A quick overview on how genes interact in different combinations:

EKAPhenotype
Em/-KB/-Dominant Black (mask not visible)
Em/-kbr/-Ay/-Sable + Mask + Brindle
Em/-kbr/-Ays/-Shaded Sable + Mask + Brindle
Em/-kbr/-aw/-Agouti + Mask + Brindle
Em/-kbr/-at/-Tan Point + Mask + Brindle
Em/-kbr/-asa/-Saddle Pattern + Mask + Brindle
Em/-kbr/-a/aRecessive Black + Mask
Em/-ky/kyAy/-Sable + Mask
Em/-ky/kyAys/-Shaded Sable + Mask
Em/-ky/kyaw/-Agouti + Mask
Em/-ky/kyat/-Tan Point + Mask
Em/-ky/kyasa/-Saddle Pattern + Mask
Em/-ky/kya/aRecessive Black + Mask
E/-KB/-Dominant Black
E/-kbr/-Ay/-Sable + Brindle
E/-kbr/-Ays/-Shaded Sable + Brindle
E/-kbr/-aw/-Agouti + Brindle
E/-kbr/-at/-Brindlepoint
E/-kbr/-asa/-Saddle Pattern + Brindle
E/-kbr/-a/aRecessive Black
E/-ky/kyAy/-Sable
E/-ky/kyAys/-Shaded Sable
E/-ky/kyaw/-Agouti
E/-ky/kyat/-Tan Point
E/-ky/kyasa/-Saddle Pattern
E/-ky/kya/aRecessive Black
eA/-
eG/-
eH/-
KB/-KB domino, phenotype can vary
eA/-
eG/-
eH/-
kbr/-Brindle Domino, phenotype can vary
eA/-
eG/-
eH/-
ky/kyAy/-
Ays/-
Sable Domino
eA/-
eG/-
eH/-
ky/kyaw/-Agouti Domino, phenotype can vary
eA/-
eG/-
eH/-
ky/kyasa/-Saddle Domino, phenotype can vary
eA/-
eG/-
eH/-
ky/kyat/-Tan Point Domino, phenotype can vary
eA/-
eG/-
eH/-
ky/kya/aRecessive Black Domino, phenotype can vary
e/eRecessive Red

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[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 dogIncorporating 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