title: Neomorphic agouti mutations in obese yellow mice.
abstract: Several dominant mutations of the mouse agouti coat colour gene have pleiotropic effects that include obesity and a yellow coat. The Ay allele is caused by a large deletion that affects the expression of several contiguous genes. We show that three other obesity-associated agouti mutations, Aiy, Asy and Avy, are due to different molecular alterations that result in ubiquitous expression of a chimaeric RNA that encodes a normal agouti protein. The Aiy and Avy alleles are caused by insertion of an intracisternal A particle element 1 kb or 100 kb, respectively, upstream of agouti coding sequences. These results provide a model for other genes that show allele-specific imprinting, and demonstrate that molecular mechanisms typically responsible for activation of proto-oncogenes can also lead to other disease phenotypes.
authors.affiliation: Department of Pediatrics, Stanford School of Medicine, California 94305.
authors.forename: D M
authors.initials: DM
authors.lastname: Duhl
authors.forename: H
authors.initials: H
authors.lastname: Vrieling
authors.forename: K A
authors.initials: KA
authors.lastname: Miller
authors.forename: G L
authors.initials: GL
authors.lastname: Wolff
authors.forename: G S
authors.initials: GS
authors.lastname: Barsh
mesh_terms: D054366:Agouti Signaling Protein; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006200:Hair Color / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008820:Mice, Obese / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics*
chemical_list: D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C515183:a protein, mouse