Metabolic characterization of a mouse deficient in all known leptin receptor isoforms.

Abstract

We have characterized a newly generated mouse model of obesity, a mouse strain deficient in all five previously described leptin receptor isoforms. These transgenic mice, named the db (333)/db (333) mice, were identified from an ENU mutagenesis screen and carry a point mutation in the seventh exon of the db gene encoding the leptin receptor, resulting in a premature stop codon (Y(333)Stop) and gene product that lacks STAT signaling domains. db (333)/db (333) mice have a morbidly obese phenotype, with body weights diverging from wild type as early as 4 weeks of age (P < 0.05). To determine the contribution of the short isoforms of the leptin receptor in this metabolic phenotype, we performed an extensive metabolic characterization of the db (333)/db (333) mouse in relation to the well-characterized db/db mouse lacking only the long form of the leptin receptor. db (333)/db (333) mice have similar endocrine and metabolic parameters as previously described in other leptin receptor transgenic mice including db/db mice that lack only the long isoform of the leptin receptor. However, db (333)/db (333) mice show a subtle trend toward higher body weight and insulin levels, lower oxygen, carbon dioxide production, respiratory exchange ratio (RER), and temperature than db/db mice suggesting the short isoforms may play an additional role in energy homeostasis.

• Authors: Olivia Osborn, Manuel Sanchez-Alavez, Sara E Brownell, Brendon Ross, Joe Klaus, Jeffrey Dubins, Bruce Beutler, Bruno Conti, Tamas Bartfai
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 30 Issue 1 Pg. 23-33 (Jan 2010) ISSN: 1573-6830 [Electronic] United States
• PMID: 19582570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Nonsense
• Insulin
• Leptin
• Protein Isoforms
• Receptors, Leptin
• leptin receptor, mouse
• Carbon Dioxide

Topics

• Animals
• Base Sequence
• Body Temperature (drug effects)
• Body Weight (drug effects)
• Carbon Dioxide (metabolism)
• Codon, Nonsense (genetics)
• DNA Mutational Analysis
• Endocrine Glands (drug effects, metabolism)
• Glucose Tolerance Test
• Hyperphagia (complications)
• Inflammation (complications, pathology)
• Insulin (pharmacology)
• Leptin (administration & dosage, pharmacology)
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Molecular Sequence Data
• Motor Activity (drug effects)
• Obesity (complications, metabolism, pathology)
• Oxygen Consumption (drug effects)
• Phenotype
• Protein Isoforms (deficiency, genetics, metabolism)
• Receptors, Leptin (deficiency, genetics, metabolism)
• Respiration (drug effects)