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Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor
S C Chua1, W K Chung, X S Wu-Peng
1Laboratory of Human Behavior and Metabolism, Rockefeller University, New York 10021, USA.
Abstract:
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.
Insights
The obese (ob) and diabetes (db) genes are crucial for body weight regulation. This study confirms that the db gene encodes the leptin receptor (OB-R), validating the leptin signaling pathway.
Area of Science:
- Genetics
- Physiology
- Molecular Biology
Background:
- Mutations in obese (ob) and diabetes (db) genes in mice cause similar metabolic phenotypes.
- A proposed pathway suggests ob encodes a ligand and db encodes its receptor for body weight regulation.
- The cloning of ob revealed it encodes leptin, a secreted protein that binds to the leptin receptor (OB-R).
Purpose of the Study:
- To genetically identify the gene responsible for the diabetes (db) phenotype.
- To determine if the db gene encodes the leptin receptor (OB-R).
Main Methods:
- Genetic mapping in mice.
- Genomic analysis.
Main Results:
- The mouse db gene, rat fatty gene, and the gene encoding the OB-R were found to be identical.
- This identifies the db gene as the specific gene for the leptin receptor.
Conclusions:
- The diabetes (db) gene encodes the leptin receptor (OB-R).
- This confirms a critical component of the leptin signaling pathway regulating body weight.