A candidate gene for the mouse mutation tubby

Noben-Trauth, Konrad; Naggert, Juergen K; North, Michael A.; Nishina, Patsy M.

doi:10.1038/380534a0

Cited by 317 publications

(142 citation statements)

References 18 publications

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“…Several mutations in mouse genes that lead to obesity have recently been characterized at the molecular level (1)(2)(3)(4)(5)(6)(7)(8). Further analysis of these genes and the use of mouse lines with mutations in these genes provides an opportunity to identify new therapeutic targets for the treatment of human obesity.…”

mentioning

confidence: 99%

Combined effects of insulin treatment and adipose tissue-specific agouti expression on the development of obesity

Mynatt

Miltenberger

Klebig

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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The agouti gene product is a secreted protein that acts in a paracrine manner to regulate coat color in mammals. Several dominant mutations at the agouti locus in mice cause the ectopic, ubiquitous expression of agouti, resulting in a condition similar to adult-onset obesity and non-insulin-dependent diabetes mellitus. The human agouti protein is 85% homologous to mouse agouti; however, unlike the mouse agouti gene, human agouti is normally expressed in adipose tissue. To address whether expression of agouti in human adipose tissue is physiologically relevant, transgenic mice were generated that express agouti in adipose tissue. Similar to most humans, these mice do not become obese or diabetic. However, we found that daily insulin injections significantly increased weight gain in the transgenic lines expressing agouti in adipose tissue, but not in nontransgenic mice. These results suggest that insulin triggers the onset of obesity and that agouti expression in adipose tissue potentiates this effect. Accordingly, the investigation of agouti's role in obesity and non-insulin-dependent diabetes mellitus in mice holds significant promise for understanding the pathophysiology of human obesity.

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confidence: 99%

Combined effects of insulin treatment and adipose tissue-specific agouti expression on the development of obesity

Mynatt

Miltenberger

Klebig

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…The fat gene encodes carboxypeptide E (CPE), an enzyme involved in neuropeptide processing (Naggert et al 1995). The tubby (tub) gene is expressed in the paraventricular nucleus of the hypothalamus, a brain region known to play a role in the regulation of body weight (Kleyn et al 1996;Noben-Trauth et al 1996).…”

Section: Results and Discussion Candidate Gene Microsatellite Contentmentioning

confidence: 99%

Microsatellite Marker Content Mapping of 12 Candidate Genes for Obesity: Assembly of Seven Obesity Screening Panels for Automated Genotyping

Winick

Friedman²

1998

Genome Res.

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Twin studies, adoption studies, and studies of familial aggregation indicate that obesity has a genetic component. Whereas, the genetic factors predisposing to obesity have been elucidated for several rare syndromes, the factors responsible for obesity in the general population have remained elusive. Genetic studies of complex traits are often accelerated by the use of candidate genes. To facilitate genetic studies of human obesity, seven multiplex panels of candidate genes for obesity that are suitable for fluorescent genotyping have been assembled. The multiplex panels are composed of 66 microsatellite markers linked tightly to 16 human gene products that are of potential importance in the control of body weight or linked to syndromic forms of obesity. As part of these efforts 12 previously cloned genes have been placed on the human physical map. In addition the chromosomal location of three of these genes, ART,NYP Y6R, and PPARγ, are reported for the first time. These resources will be of use in studies to identify the genetic factors responsible for human obesity. [Figures are available at http://www.genome.org.]

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“…Tubby is the name for a strain of mice with a naturally arising loss of function mutation affecting the C-terminus in the tub gene (Kleyn et al, 1996;Noben-Trauth et al, 1996). Tubby mice develop obesity associated with insulin resistance that is likely attributable to defects in hypothalamic signaling.…”

Section: Introductionmentioning

confidence: 99%

Mutation screen of the TUB gene in patients with retinitis pigmentosa and Leber congenital amaurosis

Pauer

Traboulsi

et al. 2006

Experimental Eye Research

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TUB is the first identified member of the TULP family of four proteins with unknown function. A spontaneous mutation in murine tub causes retinal degeneration, obesity, and deafness. Mutations in another member of the TULP family, TULP1, are a cause of autosomal recessive retinitis pigmentosa (RP). These findings prompted us to investigate TUB as a candidate gene for RP and Leber congenital amaurosis (LCA). A mutation screen of the entire coding region of the TUB gene in 159 unrelated patients with autosomal recessive RP, 114 unrelated patients with simplex RP, and 21 unrelated patients with LCA uncovered 18 sequence variations. Of these, seven were missense mutations, six were isocoding changes, and five were intronic polymorphisms. All seven missense mutations were identified as heterozygous changes and no defect could be found in the other allele. None of the isocoding variants or intronic polymorphisms are predicted to create or destroy splice donor or acceptor sites based on splice-site prediction software. Although variant alleles of the TUB gene were found, none could be definitively associated with a specific retinal disease.

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A candidate gene for the mouse mutation tubby

Cited by 317 publications

References 18 publications

Combined effects of insulin treatment and adipose tissue-specific agouti expression on the development of obesity

Combined effects of insulin treatment and adipose tissue-specific agouti expression on the development of obesity

Microsatellite Marker Content Mapping of 12 Candidate Genes for Obesity: Assembly of Seven Obesity Screening Panels for Automated Genotyping

Mutation screen of the TUB gene in patients with retinitis pigmentosa and Leber congenital amaurosis

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