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

Cell Mol Neurobiol. 2010 Jan;30(1):23-33. doi: 10.1007/s10571-009-9427-x. Epub 2009 Jul 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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