The mouse mahoganoid coat color mutation disrupts a novel C3HC4 RING domain protein

AUTOR(ES)

Phan, Loan K.

FONTE

American Society for Clinical Investigation

RESUMO

The mouse coat color mutant mahoganoid (md) darkens coat color and decreases the obesity of Ay mice that ectopically overexpress agouti-signaling protein. The phenotypic effects of md are similar to those of the recently identified coat color mutant mahogany (Atrnmg). We report the positional cloning of mahoganoid, encoding a novel 494–amino acid protein containing a C3HC4 RING (really interesting new gene) domain that may function as an E3 ubiquitin ligase. The mutations in the mahoganoid allelic series (md, md2J, md5J) are all due to large retroviral insertions. In md and md2J, the result is minimal expression of the normal size transcripts in all tissues examined. Unlike Atrnmg/Atrnmg animals, we observe no evidence of neurological deficit or neuropathology in md/md mice. Body weight and body mass index (a surrogate for adiposity) measurements of B6.C3H-md-A md/+ and md/md animals on 9% and 45% kcal fat diets indicate that mahoganoid does not suppress body weight in B6.C3H animals in a gene dose-dependent fashion.

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