Oral communication, iL7

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Mouse models for studying pigment cell biology and pigmentary diseases

Almost four hundred loci have been directly or indirectly already associated with the biology of pigment cells. Most of these loci have been detected, primarily, as mouse coat color mutants and about half of them remain to be cloned. These mouse mutants represent useful animal models for the understanding of the corresponding pigmentary diseases. This is the case of albinism, where mutations in up to 14 genes have been associated to the different types of albinism. These genes include obvious candidates, directly involved with melanin biosynthesis (Tyr, Tyrp1, Tyrp2, Pmel, Slc45a2,…). A number of additional genes appear related to the mechanisms of proliferation, differentiation and/or migration of melanocytes (Mitf, Edn3, Ednrb, Kit, Kitl, Sox10,…) and their mutations usually result in “white spotting” phenotype. Other proteins are fundamental for the biology of melanosomes. When the genes encoding these proteins are mutated a complex phenotype emerges affecting pigment cells and other cell types, where the biogenesis of lysosomal-related organelles is altered. These include all Hermansky-Pudlak syndrome-related genes (Ap3b1, Bloc1s3, Hps1, Hps3, Hps4, Hps5, Hps6…), the Chediak-Higashi syndrome locus (Lyst) and two cases of albinism (Oca2, Gpr143), among other loci. Some examples of mutations altering melanosomal intracellular movements include Myo5a and Rab27a, mutated in the Griscelli Syndrome. Other loci control the ratio between eumelanin versus pheomelanin, such as the locus agouti (A), or its receptor Mc1R, whose mutations are commonly associated to red-hair phenotype and increased risk to develop melanoma. Mutations in some genes may also display some alterations in pigmentations, however these are normally secondary to an underlying more severe defect, such as Atp7a and Atp7b loci, causing systemic effects and mutated in Menkes and Wilson diseases, respectively. The “Coat Color Mutants” web page (www.espcr.org/micemut) has an updated list of all known pigmentary-related genes, and their corresponding mouse models. Finally, mice are specially suited animal models for studying pigmentary diseases, due to the mouse genetic toolbox enabling researchers to produce genetically-modified mice (transgenic and knockout) with specific mutations reproducing those found in humans. This talk will discuss a number of examples of spontaneous and targeted mouse mutations that have been instrumental for our current understanding of human pigmentary diseases.

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