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Neomorphic agouti mutations in obese yellow mice

Nature Genetics volume 8, pages 59–65 (1994)Cite this article

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.

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Author information

Author notes

  1. Harry Vrieling

    Present address: MGC Department of Radiation Genetics and Chemical Mutagenesis, Wassenaarseweg 72, 2333 AL, Leiden, The Netherlands

Authors and Affiliations

  1. Department of Pediatrics and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, 94305, USA

    David M. J. Duhl, Harry Vrieling, Kimberly A. Miller & Gregory S. Barsh

  2. National Center for Toxicological Research, Food and Drug Administration, U.S. Department of Health and Human Services, Jefferson, Arkansas, 72079, USA

    George L. Wolff

Authors
  1. David M. J. Duhl
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  2. Harry Vrieling
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  3. Kimberly A. Miller
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  4. George L. Wolff
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  5. Gregory S. Barsh
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Duhl, D., Vrieling, H., Miller, K. et al. Neomorphic agouti mutations in obese yellow mice. Nat Genet 8, 59–65 (1994). https://doi.org/10.1038/ng0994-59

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