NONcNZO10/LtJ is a recombinant congenic strain developed at The Jackson Laboratory to model human obesity-induced Type 2 diabetes and Metabolic Syndrome. Type 2 diabetes in males of this strain results from polygenic interactions producing a moderate obesity rather than the massive obesity elicited by mutations in the leptin/leptin receptor axis. Unlike mice with monogenic obesity syndromes, NONcNZO10/LtJ males do not exhibit hypercorticism, are not hyperphagic, and show no obvious thermoregulatory defects. Male mice weaned onto LabDiet® 5K20 (a chow diet containing 10-11% fat by weight) develop visceral obesity, maturity-onset hyperglycemia, dyslipidemia, moderate liver steatosis, and pancreatic islet atrophy.
Dr. Edward Leiter, The Jackson Laboratory
Genetic Background | Generation |
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002423 NON/ShiLtJ |
N1F17p+F14
|
Onset of hyperglycemia occurs between 10-12 on a 10-11% fat (wt/wt) chow diet with greater than 85% diabetic by 18 weeks. Males exhibit increased serum triglycerides, moderate to severe liver steatosis and pancreatic islet atrophy similar to NZO/HlLt males. Serum insulin and leptin values are significantly lower than in NZO/HlLt, and are only moderately elevated above those recorded in NON/ShiLtJ males. Unlike the very obese NZO/HlLt mice, NONcNZO10/LtJ mice do not exhibit hyperphagia or hypercorticism and are much easier to breed. Although NONcNZO10/LtJ males develop only a moderate level of obesity compared to NZO/HlLt males, the interaction with known diabetogenic QTL from the NON/ShiLtJ strain produce an earlier onset and higher prevalence of chronic hyperglycemia than observed in NZO/HlLt males.
NONcNZO10/LtJ is differentially sensitive to adverse hepatic side effects of thiazolidinediones and may be useful for pharmac ogenetic analysis. This strain represents a model of polygenic obesity and obesity-induced diabetes (diabesity).
Note that the diabetes phenotype originally characterized by Dr. Leiter in his research vivarium was performed with mice fed a 6% wt/wt diet. After the strain was rederived it was experimentally determined that it is essential to feed the mice a higher fat diet to force penetrance of the diabetes phenotype.
A recombinant congenic developed by introgressing six known diabesity QTL from the Type 2 diabetes-prone and obese NZO/HlLt inbred strain into the nominally nonobese and diabetes-resistant NON/Lt strain background. NZO-derived QTL include those marked by D1Mit411, D5Mit7, D11Mit261/D11Mit41, D12Mit231 and D15Mit159.
Currently there are no related genes or alleles for this strain.
As of March 2015, mice in breeding are maintained on LabDiet® 5K0Q [6% fat].
Offspring are weaned onto and maintained on LabDiet® 5K20 [minimum 10% fat].
When using the NONcNZO10/LtJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #004456 in your Materials and Methods section.
Service/Product | Description | Price |
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Inbred, 1 pair minimum will be supplied |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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