NONcNZO10/LtJ

Stock number: 004456
Strain synonyms: RCS-10
Research areas: Diabetes and Obesity Research

Description

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.

Detailed description

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.

Development

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.