Mice homozygous for the obese spontaneous mutation, (Lepob commonly referred to as ob or ob/ob) exhibit obesity hyperphagia, a diabetes-like syndrome of hyperglycemia, glucose intolerance, elevated plasma insulin, subfertility, impaired wound healing, and an increase in hormone production from both pituitary and adrenal glands. They are also hypometabolic and hypothermic. The obesity is characterized by an increase in both number and size of adipocytes. Although hyperphagia contributes to the obesity, homozygotes gain excess weight and deposit excess fat even when restricted to a diet sufficient for normal weight maintenance in lean mice. Hyperinsulinemia does not develop until after the increase body weight and is probably the result of it. Homozygotes do have an abnormally low threshold for stimulation of pancreatic islet insulin secretion even in very young preobese animals. As is the case with mice carrying the diabetes mutation (Leprdb), manifestation of the diabetic syndrome is strikingly dependent on genetic background. Lepob homozygotes on the BTBR background develop diabetes at six weeks (males), and eight weeks (females). Hyperglycemia is severe and progressive with a fasting plasma glucose of 400 mg/dl at 10 weeks (Stoehr et al., 2000). In contrast to homozygotes on the C57BL/6 background, BTBR homozygotes develop extreme obesity (Stoehr et al., 2004) and progressive hypertriglyceridemia (Lan et al., 2003). Hepatic lipogenesis is not increased and homozygotes do not develop hepatic steatosis (Lan et al., 2003). Males remain hyperinsulinemic although insulin levels and islet mass are much reduced (Stoehr personal communication). Two modifier loci (Mobe1, Mobe2, formerly, Moo1 and Moo2) regulate total fat mass. BTBR alleles of these loci semi-dominantly increase body mass (Stoehr et al., 2004).
The obese mutation, ob, arose spontaneously at The Jackson Laboratory, Bar Harbor, Maine in 1949. The ob allele from B6.V-Lepob/J was introgressed into BTBR T+ tf/J using a marker-assisted backcrossing program for six generations at the University of Wisconsin, Madison (Stoehr, 2000). The donating investigator reports that no C57BL/6J alleles were detected with the exception of a 20 cM region on chromosome 6 flanking the leptin locus. Heterozygotes were intercrossed to produce mice homozygous for ob. This strain was donated to The Jackson Laboratory in 2003 and the backcross will be continued to N10.
In 2019, the live colony had been backcrossed to the BTBR inbred strain (Stock No. 002282) for a total of 13 generations and then intercrossed together for at least 18 generations.
|Allele Type||Spontaneous (Null/Knockout)|
|Allele Synonym(s)||ob; ob/ob|
|Gene Symbol and Name||Lep, leptin|
|Strain of Origin||STOCK Mlphln a Tgfawa1 Cdh23v Ednrbs|
|Molecular Note||Sequencing of RT-PCR products revealed a nonsense mutation in arginine codon 105 (p.R105*) resulting from a C-to-T point mutation. The 16 kDa leptin protein, expressed predominantly in adipose tissue of normal mice, is missing from homozygous mutant mice (J:29081).|
This line is maintained by mating heterozygous mice.
When using the BTBR obese mouse strain in a publication, please cite the originating article(s) and include JAX stock #004824 in your Materials and Methods section.
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