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.
Osborn
Olivia
O
Molecular and Integrative Neurosciences Department, The Harold L. Dorris Neurological Research Institute, The Scripps Research Institute, La Jolla, CA 92037, USA. olivia1@scripps.edu
Sanchez-Alavez
Manuel
M
Brownell
Sara E
SE
Ross
Brendon
B
Klaus
Joe
J
Dubins
Jeffrey
J
Beutler
Bruce
B
Conti
Bruno
B
Bartfai
Tamas
T
D000818:Animals; D001483:Base Sequence; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D018389:Codon, Nonsense / Q000235:genetics; D004252:DNA Mutational Analysis; D004702:Endocrine Glands / Q000187:drug effects / Q000378:metabolism; D005951:Glucose Tolerance Test; D006963:Hyperphagia / Q000150:complications; D007249:Inflammation / Q000150:complications / Q000473:pathology; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects; D010641:Phenotype; D020033:Protein Isoforms / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012119:Respiration / Q000187:drug effects
D018389:Codon, Nonsense; D007328:Insulin; D020738:Leptin; D020033:Protein Isoforms; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D002245:Carbon Dioxide