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

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


  • Osborn O
  • Sanchez-Alavez M
  • Brownell SE
  • Ross B
  • Klaus J
  • Dubins J
  • Beutler B
  • Conti B
  • Bartfai T


Cellular and molecular neurobiology

Publication Data

January 29, 2010

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

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