The molecular basis of brown, an old mouse mutation, and of an induced revertant to wild type.

Abstract

The murine b locus encodes the tyrosinase related protein, TRP-1, a putative membrane-bound, copper-containing enzyme having about 40% amino acid identity with tyrosinase. The protein is essential for production of black rather than brown hair pigment. We show that skin of mutant brown mice contains the same amount of TRP-1 mRNA as wild type. On sequencing the coding region of the mutant mRNA we find four nucleotide differences from the wild-type (Black) sequence. Two of these differences result in different amino acid residues encoded by the brown allele. By sequencing the TRP-1 gene from a mouse in which a reversion from brown to Black has been induced by ethylnitrosourea we are able to show that only one of these amino acid changes, which substitutes a tyrosine for a conserved cysteine, is the cause of the brown phenotype. This mutation is adjacent to another cysteine at which, in the analogous position in tyrosinase a mutation results in the albino phenotype. The sequence of the revertant is the first report of DNA sequence of an ethylnitrosourea-induced genetic change in mouse.

Phylogenetic Analysis of Core Melanin Synthesis Genes Provides Novel Insights Into the Molecular Basis of Albinism in Fish

“…The oculocutaneous albinism type 3 (OCA3) of human, also known as Rufous albinism, is caused by mutations (Arg93Cys) in tyrp1 (Dessinioti et al, 2009). The mutations of tyrp1 gene also generally caused chocolate or brown coat color in many mammals and birds, like mice (Zdarsky et al, 1990), dog (Hrckova Turnova et al, 2017), chicken (Li et al, 2019), and Japanese quail (Nadeau et al, 2007).…”

Canine coat pigmentation genetics: a review

“…In the mouse and domestic cat, TYRP1 alleles responsible for brown coat colour are each associated with a different shade of brown (Jackson 1988;Zdarsky et al 1990;Javerzat & Jackson 1998;Lyons et al 2005). In the dog, however, variation in brown coat colour did not correlate with genotype at the Brown locus and is presumably regulated by another mechanism.…”

“…In the mouse and domestic cat, TYRP1 alleles responsible for brown coat colour are each associated with a different shade of brown (Jackson 1988; Zdarsky et al . 1990; Javerzat & Jackson 1998; Lyons et al . 2005).…”

Genetic Basis of Pigment Dispersion Syndrome and Pigmentary Glaucoma: An Update and Functional Insights

“…This is exemplified in the LT/SvEiJ inbred mouse, where the Tyrp1 b-lt allele, characterized by a single missense mutation in Tyrp1, is associated with iris pigment dispersion [72,73]. Similarly, the Tyrp1 b allele, with two missense mutations, leads to iris atrophy in both DBA/2J and YBR/EiJ inbred mouse strains [56,68,74]. The nm2798 spontaneous coat color variant, arising from the dopachrome tautomerase (Dct) allele Dct slt-lt3J, is also implicated in iris pigment dispersion [72].…”