International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 176 - DARK SKIN MOUSE MUTANTS REVEAL NEW GENES INVOLVED IN PIGMENTATION

McGowan K., Van Raamsdonk C, Aradhya S, Fitch K, Barsh G

Stanford University, Stanford, United States

Melanocytes undergo a series of stereotypic behaviors as they move from the neural crest to their final resting position in the skin, including migration, proliferation, programmed cell death and differentiation.  Recently, large-scale mutagenesis projects in mice have enabled our lab to use forward genetics to study a novel class of pigmentation mutants identified by dark skin (Dsk). One class of Dsk mutants, represented by Dsk3, Dsk4, Dsk6, and Dsk11 is characterized by increased epidermal pigment in non-hairy skin.  Each mutant can be identified at weaning age. While Dsk3, Dsk4 and Dsk6 homozygotes die early in embryogenesis, Dsk11 homozygotes expire within minutes of birth.  In addition, Dsk11 homozygotes are born with an open eye phenotype, and exhibit gross and histologic abnormalities consistent with pulmonary hypoplasia. Using melanocyte-specific markers, we have shown that Dsk3 animals have an increased number of epidermal melanocytes in the tail and footpad skin, whereas Dsk4, Dsk6 and Dsk11 animals have dark skin based on mechanisms independent of pigment cell number.  Each mutant maps to a unique location in the genome, and sequence variants have recently been identified in Dsk6 and Dsk11.  This group of dark skin mutants may shed light on the mechanisms that control normal variation in human skin color, a biologic process that is mediated by changes in the activity of epidermal melanocytes. 

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