Strain Name: |
BTBR.V(B6)-Lepob/WiscJ |
|---|---|
Stock Number: |
004824 |
Availability: | Repository- Live |
General Terms and Conditions |
| Genes & Alleles | Lep; Lepob; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Spontaneous Mutation Mating System Ovarian Transplant-Cross-Intercross (Female x Male) Homozygous ovarian transplant x BTBR(#2282), then obligate Heterozygote x Heterozygote Species laboratory mouse Background Strain BTBR T+ tf/J Donor Strain V via B6.V-Lepob/J H2 Haplotype b Generation N8F1+N5F1 (14-DEC-07) Appearance
black and tan, obese, tufted
Related Genotype: at/at Lepob/Lepob tf/tf
black and tan, lean, tufted
Related Genotype: at/at Lepob/+ tf/tfStrain Description
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 onthe 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).Strain Development
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.
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Lepob | ||
|---|---|---|---|
| Allele Name | obese | ||
| Common Name(s) | ob; | ||
| Strain of Origin | STOCK Mlph | ||
| Gene Symbol and Name | Lep, leptin | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | FLJ94114; OB; OBS; ob; obese; | ||
| General Note |
Homozygous obese mice are first recognizable at about 4 weeks of age. They increase in weight rapidly and may reach three times normal weight (J:13066). In addition to obesity, mutant mice exhibit hyperphagia; a diabetes-like syndrome of hyperglycemia, glucose intolerance, and elevated plasma insulin; subfertility; and increased hormone production from both pituitary and adrenal. They also have difficulty maintaining body temperature under cold conditions (J:7702). The obesity is characterized by both an increased number of adipocytes and an increase in their size (J:7702); this is in contrast to other genetic obesities in the mouse in which increase in fat depots is due entirely to cell enlargement (J:5253, J:5765). Hyperphagia may contribute tothe obesity. However, homozygotes gain excess weight and deposit excess fat even when restricted to a diet sufficient for normal lean mice, thus demonstrating an increased metabolic efficiency (J:6236). In parabiosis with normal mice, Lepob homozygotes eat less and lose weight; in parabiosis with Leprdb homozygotes, they cease eating completely and die of starvation. This is taken to mean that they have a normal response to a 'satiety' factor, presumably the leptin protein, but are unable to produce enough of it to maintain normal food intake (J:5401). Hyperinsulinemia does not develop until after the increase in food intake and is probably the result of it (J:5759). It has been shown, however, that homozygous Lepob mice have an abnormally low threshold for stimulation of pancreatic islet insulin secretion (J:14402), even in very young animals before obesity develops (J:22634). As is the case with the diabetes mutant Leprdb, manifestation of the diabetic syndrome is strikingly dependent on genetic background. On a C57BL/6 background, Lepob homozygotes develop a well compensated diabetes with only temporary and moderate hyperglycemia, marked hyperinsulinemia, and enlarged islets of Langerhans. Onthe C57BLKS background, however, they become severely diabetic with regression of the islets and early death (J:5400). Lepob homozygous mice have an impaired capacity for non-shivering thermogenesis which can be demonstrated at low temperatures as early as 10 days of age (J:12010). At 4 degrees C they rapidly become hypothermic and die within a few hours (J:5958). It has been suggested that a reduction in the energy requirement normally used for thermoregulatory heat production could be responsible for the increased metabolic efficiency noted above. That is unlikely to be the major cause of the thermoregulatory problems, however, since brief exposure of obese mice to 10 degrees C produces cold adaptation and allows indefinite survival at 4degrees C with maintenance of nearly normal body temperature (J:6756). Coleman has suggested that the hyperinsulinemia of obese mice, which increases synthetic processes and decreases degradation, might spare the energy normally spent on tissue turnover and account at least in part for the increased efficiency (J:6756). Some contribution to the effect may also come from a low basal Na+,K+ATPase activity, shown to occur in muscle of 14-day old mutants (J:6182). Heterozygotes (Lepob/+) have normal body weight, blood glucose, and plasma insulin, but can survive a prolonged fast longer than congenic wild type controls, suggesting that increased metabolic efficiency is expressed to some extent in heterozygotes (J:159). Female homozygotes are always sterile, although their ovaries respond to exogenous pituitary hormones. About 20% of male homozygotes may be transiently fertile, particularly if maintained on a restricted diet (J:7702). Cloning of the Lep gene has made possible the production of recombinant leptin. Injection of this protein into Lepob homozygotes sharply reduces body weight, decreases food intake, and increases energy expenditure. There is no effect in diabetic Leprdb homozygotes, who are resistant to effects of the Lepob mutation. Normal mice also decrease food consumption and lose weight, with an accompanying loss in body fat (J:29161). Other investigators have obtained congruent results in normal and in Lepob mice (J:29162, J:29075); leptin also reduces food intake in fasted normal mice (J:28578). Leptin treatment effects on behavior of Lepob mice suggest a direct effect on neuronal networks (J:29160). Interactions of leptin with effects of hypothalamic lesions and of the Lepr gene indicate that Lep is upstream in the pathway of adipose tissue mass regulation (J:27422). Mutant leptin produced by the Lepob mutation fails to self-regulate production of leptin mRNA, which rises to a level 4 times that in normal mice. Lean mice when fasted decrease in leptin mRNA levels, but obese animals do not (J:29081). There is a vast literature on the biochemical and physiological changes in Lepob mice, which has been reviewed by Herberg and Coleman (J:5759) and more recently by Charlton (J:7702). Many of the studies performed in adult mice may involve secondary effects of obesity rather than primary causes of it. Increased blood levels of corticosterone occur in Lepob/Lepob mice, and most of the symptoms of the obese syndrome are ameliorated by excision of the adrenal glands. The hypothalamus-pituitary-adrenal axis is dysregulated, with hyperactivity of pituitary synthesis and secretion of adrenocorticotropic hormone (ACTH), as well as hyperresponsiveness of the adrenal cortex to ACTH (J:13151). Adrenal medullary activity, on the other hand, may be decreased; a diminished urinary excretion of epinephrine in obese homozygous mice indicates reduced medullary production, although this may be a secondary effect of the obesity (J:4033). A low serum level of the thyroid hormone triiodothyronine (T3) is also characteristic of obese homozygotes. Early treatment of these mice with T3 increases oxygen consumption and temperature while reducing body fat (J:22025). T3 treatment increases oxidative metabolism in muscle, but not in brown adipose tissue or in liver (J:22377). Plasma triglyceride levels are elevated in mouse mutants considered models of non-insulin-dependent diabetes,including Lepob mutants. Cholesterol is also elevated, but the increase is primarily in high-density lipoprotein cholesterol (J:18161), so that atherosclerotic lesions are not increased (J:19043). | ||
| Molecular Note | Sequencing of RT-PCR products revealed a nonsense mutation in codon 105 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). [MGI Ref ID J:20512] [MGI Ref ID J:29081] [MGI Ref ID J:45748] | ||
Control Information
| Allele | Control | |
|---|---|---|
| Lepob | Wild-type from the colony | |
| Considerations for Choosing Controls | ||
Genotyping Protocols
Lepob
Colony Maintenance
| Diet Information | LabDiet® 5K52/5K67 |
|---|
Related Strains
Strains carrying Lepob allele
006906 B6.Cg-Lepob Ldlrtm1Her/J 000632 B6.V-Lepob/J 000696 BKS.V-Lepob/J View Strains carrying Lepob (3 strains)
Additional Web Information
Congenic Nomenclature
Animal Health Reports
Room Number FGB29
Research Applications
This mouse can be used to support research in many areas including:
Lepob relatedCardiovascular Research
Hypertriglyceridemia
Diabetes and Obesity Research
Hyperinsulinemia
Impaired Wound Healing
Insulin Resistance
Obesity With Diabetes
Endocrine Deficiency Research
Adipose Defects
Hypothalamus/Pituitary Defects
Pancreas Defects
Immunology and Inflammation Research
Immunodeficiency Associated with Other Defects
Internal/Organ Research
Adipose Defects
Metabolism Research
Mouse/Human Gene Homologs
obesity, severe, due to leptin deficiency (rare)
Reproductive Biology Research
Fertility Defects
References
Selected Reference(s)
Additional ReferencesStoehr JP; Nadler ST; Schueler KL; Rabaglia ME; Yandell BS; Metz SA; Attie AD. 2000. Genetic obesity unmasks nonlinear interactions between murine type 2 diabetes susceptibility loci Diabetes 49(11):1946-54. [PubMed: 11078464] [MGI Ref ID J:65486]
Price and Supply Information
| Strain Name: | BTBR.V(B6)-Lepob/WiscJ |
| Stock Number: | 004824 |
Price Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
Usually shipped between four and eight weeks of age. This strain is included in the Mouse Mutant Resource collection. |
| Licensing | See General Terms and Conditions below |
| Control Information | View Control Information in Strain Details. |
General Terms and Conditions
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering and Purchasing Information
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