Disease relevance of Slc45a2

• Tyrosinase processing and intracellular trafficking is disrupted in mouse primary melanocytes carrying the underwhite (uw) mutation. A model for oculocutaneous albinism (OCA) type 4 [1].
• The human ortholog of AIM-1 was originally identified as a melanocyte-restricted antigen that is recognized by autologous T cells from a patient with melanoma [2].
• Mutations at the mouse underwhite locus confer one of the most severe hypopigmentation phenotypes, similar to mutations at the pink-eyed dilution locus that is a model for type 2 oculocutaneous albinism [3].

High impact information on Slc45a2

• Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4 [4].
• Aurora-B/AIM-1 protein is, however, elevated in diploid transgenic megakaryocytes [5].
• Nevertheless, MITF links AIM-1 expression and the underwhite phenotype to a transcriptional network central to pigmentation in mammals [2].
• Mice with mutations at the underwhite locus and either the pink-eyed dilution locus or the melanocortin receptor 1 locus exhibited more severe hypopigmentation than either mutation alone, suggesting that the actions of these genes are independent [3].
• Consistent with MATP acting in a pigment cell autonomous manner, in situ hybridization analysis demonstrated expression of murine Matp in the presumptive retinal pigmented epithelium starting at E9.5, and in neural crest-derived melanoblasts starting at E10 [6].

Biological context of Slc45a2

• The oculocutaneous albinism type IV gene Matp is a new marker of pigment cell precursors during mouse embryonic development [6].
• Three-point linkage analysis established th location of Gpt-1 on chromosome 15 between uw and bt [7].
• Of these, AIM-1 kinase mRNA was severely downregulated by Mpl ligand at the onset of polyploidy in megakaryocytes [8].

Anatomical context of Slc45a2

• To characterize OCA4, we investigated the processing and sorting of melanogenic proteins in primary melanocytes derived from uw/uw mice and from wild-type mice [1].

Other interactions of Slc45a2

• We show that the uw locus is genetically distinct from Myo10, a suggested candidate gene for this mutation [9].

References