Neomorphic agouti mutations in obese yellow mice

Nat Genet. 1994 Sep;8(1):59-65. doi: 10.1038/ng0994-59.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Agouti Signaling Protein
  • Alleles
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Hair Color / genetics*
  • Intercellular Signaling Peptides and Proteins*
  • Mice
  • Mice, Obese / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Proteins / genetics*


  • Agouti Signaling Protein
  • Intercellular Signaling Peptides and Proteins
  • Proteins
  • a protein, mouse

Associated data

  • GENBANK/S74469
  • GENBANK/S74476
  • GENBANK/S74479
  • GENBANK/S74482
  • GENBANK/S74489
  • GENBANK/S74493