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Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur.
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- Author(s): Klebig ML;Klebig ML; Wilkinson JE; Geisler JG; Woychik RP
- Source:
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1995 May 23; Vol. 92 (11), pp. 4728-32.- Publication Type:
Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.- Language:
English - Source:
- Additional Information
- Source: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print Cited Medium: Print ISSN: 0027-8424 (Print) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
- Publication Information: Original Publication: Washington, DC : National Academy of Sciences
- Subject Terms: Intercellular Signaling Peptides and Proteins* ; Protein Biosynthesis*; Aging/*physiology ; Diabetes Mellitus, Type 2/*genetics ; Hair Color/*genetics ; Obesity/*genetics ; Proteins/*genetics; Agouti Signaling Protein ; Animals ; Base Sequence ; Blood Glucose/metabolism ; Chromosome Mapping ; DNA Primers ; Enhancer Elements, Genetic ; Exons ; Female ; Gene Expression ; Genes, Dominant ; Genes, Lethal ; Insulin/blood ; Introns ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Mice, Transgenic ; Molecular Sequence Data ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Weight Gain/genetics
- Abstract: Mice that carry the lethal yellow (Ay) or viable yellow (Avy) mutation, two dominant mutations of the agouti (a) gene in mouse chromosome 2, exhibit a phenotype that includes yellow fur, marked obesity, a form of type II diabetes associated with insulin resistance, and an increased susceptibility to tumor development. Molecular analyses of these and several other dominant "obese yellow" a-locus mutations suggested that ectopic expression of the normal agouti protein gives rise to this complex pleiotropic phenotype. We have now tested this hypothesis directly by generating transgenic mice that ectopically express an agouti cDNA clone encoding the normal agouti protein in all tissues examined. Transgenic mice of both sexes have yellow fur, become obese, and develop hyperinsulinemia. In addition, male transgenic mice develop hyperglycemia by 12-20 weeks of age. These results demonstrate conclusively that the ectopic agouti expression is responsible for most, if not all, of the phenotypic traits of the dominant, obese yellow mutants.
- Comments: Comment in: Proc Natl Acad Sci U S A. 1995 May 23;92(11):4721-4. (PMID: 7761389)
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- Accession Number: 0 (Agouti Signaling Protein)
0 (Blood Glucose)
0 (DNA Primers)
0 (Insulin)
0 (Intercellular Signaling Peptides and Proteins)
0 (Proteins)
0 (a protein, mouse) - Publication Date: Date Created: 19950523 Date Completed: 19950629 Latest Revision: 20191210
- Publication Date: 20240628
- Accession Number: PMC41780
- Accession Number: 10.1073/pnas.92.11.4728
- Accession Number: 7761391
- Source:
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