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Thesis - University Access Only
Master of Science (MS)
There are nearly fifty genetic loci that are responsible for the production and deposition of pigment in the hairs of the common house mouse (Mus musculus L.). Of these, the a or agouti locus of chromosome 2 provides one of the most compelling models to study the way mammalian genes are regulated. It is the agouti locus which gives the wild type house mouse it's unique two-tone yellow on black appearance. The agouti locus accomplishes this by regulating the type and amount of pigment synthesized in specialized dendritic cells found in the hair follicle. In mammals, the pigment that gives color to the hair and skin is melanin. Hence, the specialized cells that produce melanin are called melanocytes. Black and brown pigments are designated eumelanins, yellow and red pigments pheomelanin. Melanogenesis refers to the biochemical pathway that leads to the production of the two types of pigment. Hair of the wild-type agouti mouse is characterized by it's [sic] black tip, yellow subapical band, and black shaft. This unique pattern denotes a shift in the type of melanin made. In the wild type mouse the melanocytes begin making black (eumelanin) in the first three days of hair production. The cells then switch and begin producing yellow (pheomelanin) for approximately three days and then switch back to black pigment for the duration of hair growth. This black-to-yellow and yellow-to-black pattern of pigment production is called the agouti pattern, and the transition from the synthesis of one pigment to the other is termed the agouti switch. Alleles of the agouti locus are designated by their particular variation of this pigment pattern and on other pleiotropic effects related to the agouti locus. Over 18 natural and radiation induced alleles have been characterized. The AY or lethal yellow allele on the C57BL/6J background is characterized by completely yellow hair when paired with any recessive allele, and when homozygous (Ay/Ay), the developing embryos are lethal. The a or nonagouti black allele confers completely black dorsal hair when homozygous (a/a). These two alleles represent two extreme variations of the coat color phenotype controlled by the agouti locus. With respect to the wild-type agouti mouse (NA) in which melanocytes can switch from black to yellow to black, Ay/a mice appear to be stuck in the yellow phase of the agouti cycle and a/a mice cannot switch from black pigment. These two alleles also represent two different positions in the dominance hierarchy of the agouti locus. One of the more compelling aspects of the agouti locus is that it regulates melanogenesis through the follicular cells rather than autonomously within melanocytes themselves. This was demonstrated by a set of elaborate grafting experiments carried out by W. K. Silvers and E. S. Russell (1955). It is the microenvironment of the follicles in which the melanocytes reside that dictates whether eumelanin, pheomelanin, or both pigments are produced within the melanocytes. Interestingly, genotypically black melanocytes when grafted to genetically yellow follicles will synthesize yellow pigment and vice versa. These experiments document that yellow (Ay/a) and black (a/a) genotypes are capable of making black and yellow melanin, respectively if provided with the appropriate cues or signals from the hair follicle. In short because they are subject to regulation, lethal yellow (Ay/a) melanocytes posses [sic] the necessary DNA and cytoplasmic components to become unstuck and synthesize eumelanin. Another clue to the possible role of the agouti locus is the response of Ay/a hairbulb melanocytes to exogenous α-melanocyte stimulating hormone (αMSH). In yellow (Ay/a) and agouti (A/A) mice who's [sic] hair was first plucked and than [sic] received injections of MSH, the regenerating hairs were completely black (Geschwind et al., 1972). This is another indication that the melanocytes of the Ay/a mice can produce eumelanin when they receive the appropriate external signals.
Library of Congress Subject Headings
Mice -- Genetics
Melanins -- Synthesis
South Dakota State University
Kappenman, Karl E., "Investigations on the Effects of the Murine Lethal Yellow Allele (C57BL/6J) on Tyrosinase Synthesis, Abundance, Activity, and PAGE-Defined Isozymes" (1991). Electronic Theses and Dissertations. 5480.