Chromosomal localization and genomic characterization of the mouse melastatin gene (Mlsn1).
We recently described a novel gene, melastatin, whose expression is inversely correlated with melanoma aggressiveness. Chromosomal localization of this gene places it on mouse chromosome 7 and in the 15q13-q14 region of the human genome. Although expression patterns and chromosomal localization in the mouse are consistent with involvement of melastatin mutations in the mouse ruby-eye-2 defect, congenic analysis showed genetic segregation of the two loci. Cloning of the full-length human cDNA revealed a much larger transcript than we had previously identified, corresponding to a 1533-amino-acid protein product with homology to members of the transient receptor potential (Trp) family of calcium channels. The mouse melastatin gene contains 27 exons and spans at least 58 kb of genomic DNA. The promoter region of Mlsn1 contains four potential microphthalmia binding sites including an M box, a transcriptional regulatory element unique to genes with a restricted melanocytic expression pattern. A 1-kb PvuII fragment from this region was capable of driving high levels of luciferase expression in B16 melanoma cells.
Hunter
J J
JJ
Millennium Pharmaceuticals, Inc., 640 Memorial Drive, Cambridge, Massachusetts, 02139, USA.
Shao
J
J
Smutko
J S
JS
Dussault
B J
BJ
Nagle
D L
DL
Woolf
E A
EA
Holmgren
L M
LM
Moore
K J
KJ
Shyjan
A W
AW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D018076:DNA, Complementary; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007178:Inbreeding; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D050053:TRPM Cation Channels; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D050053:TRPM Cation Channels; C492059:TRPM1 protein, human; C116297:Trpm1 protein, mouse