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

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 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.

journal_name

Cell Mol Neurobiol

authors

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

doi

10.1007/s10571-009-9427-x

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

23-33

issue

1

eissn

0272-4340

issn

1573-6830

journal_volume

30

pub_type

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