Phenotypes of Mouse Diabetes and Rat Fatty Due to Mutations in the OB (Leptin) Receptor

• Published in: Science (American Association for the Advancement of Science) 1996-02, Vol.271 (5251), p.994-996
• Main Authors: Chua, Streamson C., Chung, Wendy K., Wu-Peng, X. Sharon, Zhang, Yiying, Liu, Shun-Mei, Tartaglia, Louis, Leibel, Rudolph L.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Blotting, Southern; Carrier Proteins - genetics; Cell receptors; Chromosome Mapping; Chromosomes; Classical genetics, quantitative genetics, hybrids; Cloning, Molecular; Coding; Complementary DNA; Diabetes; Diabetes mellitus; Diabetes Mellitus - genetics; DNA; DNA Mutational Analysis; Fundamental and applied biological sciences. Psychology; Genes; Genetic aspects; Genetic mapping; Genetic Markers; Genetic mutation; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genomics; Leptin; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Molecular Sequence Data; Mutation; Obesity; Obesity - genetics; Phenotype; Polymerase Chain Reaction; Proteins; Proteins - genetics; Rats; Rats, Inbred Strains; Receptors; Receptors, Cell Surface; Receptors, Cytokine - genetics; Receptors, Leptin; Rodents; Vertebrata
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.271.5251.994

Mice harboring mutations in the obese (ob) and diabetes (db) genes display similar phenotypes, and it has been proposed that these genes encode the ligand and receptor, respectively, for a physiologic pathway that regulates body weight. The cloning of ob, and the demonstration that it encodes a secreted protein (leptin) that binds specifically to a receptor (OB-R) in the brain, have validated critical aspects of this hypothesis. Here it is shown by genetic mapping and genomic analysis that mouse db, rat fatty (a homolog of db), and the gene encoding the OB-R are the same gene.