The DOI matches its Crossref record.
Phenotype of fatty Due to Gln269Pro Mutation in the Leptin Receptor (Lepr)
Abstract
The rat fatty (fa) mutation produces profound obesity of early onset caused by hyperphagia, defective nonshivering thermogenesis, and preferential deposition of energy into adipose tissue. Genetic mapping studies indicate that fa and diabetes (db) are homologous loci in the rat and mouse genomes, respectively. It has been shown that db alleles carry mutations in the Lepr (leptin receptor) gene. This paper describes a point mutation in the fatty allele of Lepr. A nucleotide substitution at position 880 (A→C) causes an amino acid substitution at position 269 (Gln → Pro). The mutation generates a novel Msp I site that cosegregates with fa in 1,028 meioses examined in obese F2 progeny from two crosses (BN×13M and WKY×13M) and is still segregating in three rat colonies. PCR-based mutagenesis was used to introduce the fa mutation into the mouse Lepr cDNA. Transient transfection studies indicate that the mutant Lepr cDNA has greatly reduced binding of leptin (Lep) at the cell surface. These data are strong evidence that the single nucleotide substitution in the fa allele of Lepr (Leprfa) is responsible for the obese phenotype.
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Citations
Cited by
Tartaglia, L. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.10.6093 · Cited by 1,289
Self-citationLeptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels
Spanswick, D., Smith, M. A., Groppi, V. E., Logan, S. D., & Ashford, M. L. J. (1997) · Nature · doi:10.1038/37379 · Cited by 628
Russell, J. C., & Proctor, S. D. (2006) · Cardiovascular Pathology · doi:10.1016/j.carpath.2006.09.001 · Cited by 317
Obesity, diabetes and the central nervous system
Porte Jr., D., Seeley, R. J., Woods, S. C., Baskin, D. G., Figlewicz, D. P., & Schwartz, M. W. (1998) · Diabetologia · doi:10.1007/s001250051002 · Cited by 186
Morton, G. J., Niswender, K. D., Rhodes, C. J., Myers, M. G., Blevins, J. E., Baskin, D. G., & Schwartz, M. W. (2003) · Endocrinology · doi:10.1210/en.2002-0115 · Cited by 158
Molecular physiology of weight regulation in mice and humans
Leibel, R. L. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.245 · Cited by 120
Self-citationSchwartz, M. W., & Niswender, K. D. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0906 · Cited by 93
Cardiac β‐adrenergic responsiveness of obese Zucker rats: The role of AMPK
Bussey, C. T., Thaung, H. P. A., Hughes, G., Bahn, A., & Lamberts, R. R. (2018) · Experimental Physiology · doi:10.1113/ep087054 · Cited by 10
Metadata
- Authors
- Chua, S. C., White, D. W., Wu-Peng, X. S., Liu, S.-M., Okada, N., Kershaw, E. E., Chung, W. K., Power-Kehoe, L., Chua, M., Tartaglia, L. A., & Leibel, R. L.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1996-08-01
- Volume
- 45
- Issue
- 8
- Pages
- 1141-1143
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2168871248
- Cited by
- 293
- References
- 0
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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