CHROMOSOMAL LOCALIZATION AND GENOMIC CHARACTERIZATION OF THE MOUSE MELASTATIN GENE (MLSN1)

We recently described a novel gene, melastatin, whose expression is in versely correlated with melanoma aggressiveness. Chromosomal localizat ion of this gene places it on mouse chromosome 7 and in the 15q13-q14 region of the human genome. Although expression patterns and chromosom al localization in the mouse are consistent with involvement of melast atin mutations in the mouse ruby-eye-a defect, congenic analysis showe d genetic segregation of the two loci. Cloning of the full-length huma n cDNA revealed a much larger transcript than we had previously identi fied, corresponding to a 1533-amino-acid protein product with homology to members of the transient receptor potential (Trp) family of calciu m channels. The mouse melastatin gene contains 27 exons and spans at l east 58 kb of genomic DNA. The promoter region of Mlsn1 contains four potential microphthalmia binding sites including an M box, a transcrip tional regulatory element unique to genes with a restricted melanocyti c expression pattern. A l-kb PvuII fragment from this region was capab le of driving high levels of luciferase expression in B16 melanoma cel ls. (C) 1998 Academic Press.