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

http://www.ncbi.nlm.nih.gov/pubmed/19582570

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.

Pubmed ID: 19582570 RIS Download

Mesh terms: Animals | Base Sequence | Body Temperature | Body Weight | Carbon Dioxide | Codon, Nonsense | DNA Mutational Analysis | Endocrine Glands | Glucose Tolerance Test | Hyperphagia | Inflammation | Insulin | Leptin | Mice | Mice, Inbred C57BL | Mice, Obese | Molecular Sequence Data | Motor Activity | Obesity | Oxygen Consumption | Phenotype | Protein Isoforms | Receptors, Leptin | Respiration

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Associated grants

  • Agency: NIA NIH HHS, Id: R01 AG028040
  • Agency: NIA NIH HHS, Id: R01 AG028040-01A1
  • Agency: NIA NIH HHS, Id: R01 AG028040-02
  • Agency: NIA NIH HHS, Id: R01 AG028040-03

Mouse Genome Informatics (Data, Gene Annotation)

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