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

Olivia Osborn, Manuel Sanchez-Alavez, Sara E. Brownell, Brendon Ross, Joe Klaus, Jeffrey Dubins, Bruce Beutler, Bruno Conti, Tamas Bartfai

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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 (Y333Stop) 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.

Original languageEnglish (US)
Pages (from-to)23-33
Number of pages11
JournalCellular and Molecular Neurobiology
Issue number1
StatePublished - Jan 2010
Externally publishedYes


  • Db /db
  • Db/db
  • Diabetes
  • Insulin resistance
  • Leptin
  • Leptin receptor
  • Ob-Rb
  • Obesity

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology


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