The mouse mahoganoid coat color mutation disrupts a novel C3HC4 RING domain protein.
The mouse coat color mutant mahoganoid (md) darkens coat color and decreases the obesity of A(y) mice that ectopically overexpress agouti-signaling protein. The phenotypic effects of md are similar to those of the recently identified coat color mutant mahogany (Atrn(mg)). 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, md(2J), md(5J)) are all due to large retroviral insertions. In md and md(2J), the result is minimal expression of the normal size transcripts in all tissues examined. Unlike Atrn(mg/)Atrn(mg) 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. Mahoganoid effects on energy homeostasis are, therefore, most evident in the circumstances of epistasis to hypothalamic overexpression of ASP in A(y) and possible other obesity-causing mutations.
Phan
Loan K
LK
Division of Molecular Genetics, Department of Pediatrics, Institute of Human Nutrition, Columbia University, New York, New York, USA.
Lin
Feng
F
LeDuc
Charles A
CA
Chung
Wendy K
WK
Leibel
Rudolph L
RL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009765:Obesity / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012880:Skin Pigmentation / Q000235:genetics* / Q000502:physiology; D014018:Tissue Distribution; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; D018076:DNA, Complementary; D012333:RNA, Messenger; C470690:MGRN1 protein, human; C470689:Mgrn1 protein, mouse; D044767:Ubiquitin-Protein Ligases