Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Phan LK

PROVIDER: S-EPMC151815 | biostudies-literature | 2002 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Phan Loan K LK Lin Feng F LeDuc Charles A CA Chung Wendy K WK Leibel Rudolph L RL

The Journal of clinical investigation 20021101 10

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 a ...[more]

PMID: 12438443

Similar Datasets

Project description:BACKGROUND: The Silver coat color, also called Silver dapple, in the horse is characterized by dilution of the black pigment in the hair. This phenotype shows an autosomal dominant inheritance. The effect of the mutation is most visible in the long hairs of the mane and tail, which are diluted to a mixture of white and gray hairs. Herein we describe the identification of the responsible gene and a missense mutation associated with the Silver phenotype. RESULTS: Segregation data on the Silver locus (Z) were obtained within one half-sib family that consisted of a heterozygous Silver colored stallion with 34 offspring and their 29 non-Silver dams. We typed 41 genetic markers well spread over the horse genome, including one single microsatellite marker (TKY284) close to the candidate gene PMEL17 on horse chromosome 6 (ECA6q23). Significant linkage was found between the Silver phenotype and TKY284 (theta = 0, z = 9.0). DNA sequencing of PMEL17 in Silver and non-Silver horses revealed a missense mutation in exon 11 changing the second amino acid in the cytoplasmic region from arginine to cysteine (Arg618Cys). This mutation showed complete association with the Silver phenotype across multiple horse breeds, and was not found among non-Silver horses with one clear exception; a chestnut colored individual that had several Silver offspring when mated to different non-Silver stallions also carried the exon 11 mutation. In total, 64 Silver horses from six breeds and 85 non-Silver horses from 14 breeds were tested for the exon 11 mutation. One additional mutation located in intron 9, only 759 bases from the missense mutation, also showed complete association with the Silver phenotype. However, as one could expect to find several non-causative mutations completely associated with the Silver mutation, we argue that the missense mutation is more likely to be causative. CONCLUSION: The present study shows that PMEL17 causes the Silver coat color in the horse and enable genetic testing for this trait.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets