Cellular and Molecular Neurobiology

, Volume 30, Issue 1, pp 23–33

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
Original Paper

DOI: 10.1007/s10571-009-9427-x

Cite this article as:
Osborn, O., Sanchez-Alavez, M., Brownell, S.E. et al. Cell Mol Neurobiol (2010) 30: 23. doi:10.1007/s10571-009-9427-x

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 db333/db333 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. db333/db333 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 db333/db333 mouse in relation to the well-characterized db/db mouse lacking only the long form of the leptin receptor. db333/db333 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, db333/db333 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.

Keywords

LeptinLeptin receptorOb–RbObesitydb/dbdb333/db333DiabetesInsulin resistance

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Olivia Osborn
    • 1
  • Manuel Sanchez-Alavez
    • 1
  • Sara E. Brownell
    • 1
  • Brendon Ross
    • 1
  • Joe Klaus
    • 1
  • Jeffrey Dubins
    • 3
  • Bruce Beutler
    • 2
  • Bruno Conti
    • 1
  • Tamas Bartfai
    • 1
  1. 1.Molecular and Integrative Neurosciences Department, The Harold L. Dorris Neurological Research InstituteThe Scripps Research InstituteLa JollaUSA
  2. 2.Department of GeneticsThe Scripps Research InstituteLa JollaUSA
  3. 3.Pfizer ResearchGrotonUSA