ArticleGenetics1996
Coupled site-directed mutagenesis/transgenesis identifies important functional domains of the mouse agouti protein.
Article in Genetics, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Construction of MC1R and ASIP Eukaryotic Expression Vector and its Regulation of Plumage Color in Japanese Quail (The journal of poultry science · 2019Article
- A missense mutation in the agouti signaling protein gene (ASIP) is associated with the no light points coat phenotype in donkeys.Genetics, selection, evolution : GSE · 2015Article
- Article
- Transient ectopic overexpression of agouti-signalling protein 1 (asip1) induces pigment anomalies in flatfish.PloS one · 2012Article
- Article
- Genetics of Sex-linked yellow in the Syrian hamster.Genetics · 2009Article
- Investigation of the role of the agouti signaling protein gene (ASIP) in coat color evolution in primates.Mammalian genome : official journal of the International Mammalian Genome Society · 2006Article
- Molecular and phenotypic analysis of 25 recessive, homozygous-viable alleles at the mouse agouti locus.Genetics · 2002Article
- An agouti mutation lacking the basic domain induces yellow pigmentation but not obesity in transgenic mice.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
- Characterization of genes modulated during pheomelanogenesis using differential display.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- Modulation of murine melanocyte function in vitro by agouti signal protein.The EMBO journal · 1997Article
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Authors and funding
8 authors.
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Abstract
The agouti locus encodes a novel paracrine signaling molecule containing a signal sequence, an N-linked glycosylation site, a central lysine-rich basic domain, and a C-terminal tail containing 10 cysteine (Cys) residues capable of forming five disulfide bonds. When overexpressed, agouti causes a number of pleiotropic effects including yellow coat and adult-onset obesity. Numerous studies suggest that agouti causes yellow coat color by antagonizing the binding of alpha-melanocyte-stimulating hormone (alpha-MSH) to the alpha-MSH-(Melanocortin-1) receptor. With the goal of identifying functional domains of agouti important for its diverse biological activities, we have generated 14 agouti mutations by in vitro site-directed mutagenesis and analyzed these mutations in transgenic mice for their effects on coat color and obesity. These studies demonstrate that the signal sequence, the N-linked glycosylation site, and the C-terminal Cys residues are important for full biological activity, while at least a portion of the lysine-rich basic domain is dispensable for normal function. They also show that the same functional domains of agouti important to coat color determination are important for inducing obesity, consistent with the hypothesis that agouti induces obesity by antagonizing melanocortin binding to other melanocortin receptors.
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