Overview

Also Known As:RCS-10

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.

Donating Investigator

Dr. Edward Leiter, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
002423 NON/ShiLtJ	N1F17p+F14 (2019-07-16 00:00:00)

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Research Applications

Diabetes and Obesity Research

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Base Price

Starting at:

$278.00 Domestic price for female 4-week

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Details

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.

Control Suggestions

Please Inquire (The controls recommended for NONcNZO10/LtJ depend on its intended use. The parental line, NON/ShiLtJ (Stock No. 002423), provides a genetic background control (88% homology). On a 10-11% fat diet, which is available for purchase, this strain exhibits moderate obesity and impaired glucose tolerance, but does not develop hyperglycemia. Like NON/ShiLtJ, SWR/J (Stock No. 000689) is a Swiss-derived inbred. SWR/J mice are resistant to diet-induced obesity and do not exhibit impaired glucose tolerance. A third option, NONcNZO5/LtJ (Stock No. 004455), is available only in limited quantities, however, males of this strain exhibit moderate obesity, and both sexes are diabetes resistant. )

Additional Information

Considerations for Choosing Controls

Selected References

Cho YR; Kim HJ; Park SY; Ko HJ; Hong EG; Higashimori T; Zhang Z; Jung DY; Ola MS; Lanoue KF; Leiter EH; Kim JK. 2007. Hyperglycemia, maturity-onset obesity, and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2 diabetes. Am J Physiol Endocrinol Metab 293(1):E327-36PubMed: 17616608 MGI: J:122834
Fang RC; Kryger ZB; Buck DW 2nd; De la Garza M; Galiano RD; Mustoe TA. 2010. Limitations of the db/db mouse in translational wound healing research: Is the NONcNZO10 polygenic mouse model superior? Wound Repair Regen 18(6):605-13PubMed: 20955341 MGI: J:165705
Leiter EH; Reifsnyder PC. 2004. Differential levels of diabetogenic stress in two new mouse models of obesity and type 2 diabetes. Diabetes 53 Suppl 1:S4-11PubMed: 14749259 MGI: J:109841
Leiter EH; Reifsnyder PC; Flurkey K; Partke HJ; Junger E; Herberg L. 1998. NIDDM genes in mice: deleterious synergism by both parental genomes contributes to diabetogenic thresholds. Diabetes 47(8):1287-95PubMed: 9703330 MGI: J:48957
Reifsnyder PC; Churchill G; Leiter EH. 2000. Maternal environment and genotype interact to establish diabesity in mice. Genome Res 10(10):1568-78PubMed: 11042154 MGI: J:65256
Reifsnyder PC; Leiter EH. 2002. Deconstructing and reconstructing obesity-induced diabetes (diabesity) in mice. Diabetes 51(3):825-32PubMed: 11872687 MGI: J:75024
Taylor BA; Wnek C; Schroeder D; Phillips SJ. 2001. Multiple obesity QTLs identified in an intercross between the NZO (New Zealand obese) and the SM (small) mouse strains. Mamm Genome 12(2):95-103PubMed: 11210195 MGI: J:67838
Watkins SM; Reifsnyder PR; Pan HJ; German JB; Leiter EH. 2002. Lipid metabolome-wide effects of the PPARgamma agonist rosiglitazone. J Lipid Res 43(11):1809-17PubMed: 12401879 MGI: J:109849

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Genetics

Currently there are no related genes or alleles for this strain.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
- Hyperglycemia
  - males
- Type 2 Diabetes (NIDDM)
  - males
- Obesity Without Diabetes
  - females
- Obesity With Diabetes
  - moderate, males

Mammalian Phenotype Terms by Genotype

Phenotype Information

References

Cho YR; Kim HJ; Park SY; Ko HJ; Hong EG; Higashimori T; Zhang Z; Jung DY; Ola MS; Lanoue KF; Leiter EH; Kim JK. 2007. Hyperglycemia, maturity-onset obesity, and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2 diabetes. Am J Physiol Endocrinol Metab 293(1):E327-36PubMed: 17616608 MGI: J:122834
Fang RC; Kryger ZB; Buck DW 2nd; De la Garza M; Galiano RD; Mustoe TA. 2010. Limitations of the db/db mouse in translational wound healing research: Is the NONcNZO10 polygenic mouse model superior? Wound Repair Regen 18(6):605-13PubMed: 20955341 MGI: J:165705
Leiter EH; Reifsnyder PC. 2004. Differential levels of diabetogenic stress in two new mouse models of obesity and type 2 diabetes. Diabetes 53 Suppl 1:S4-11PubMed: 14749259 MGI: J:109841
Leiter EH; Reifsnyder PC; Flurkey K; Partke HJ; Junger E; Herberg L. 1998. NIDDM genes in mice: deleterious synergism by both parental genomes contributes to diabetogenic thresholds. Diabetes 47(8):1287-95PubMed: 9703330 MGI: J:48957
Reifsnyder PC; Churchill G; Leiter EH. 2000. Maternal environment and genotype interact to establish diabesity in mice. Genome Res 10(10):1568-78PubMed: 11042154 MGI: J:65256
Reifsnyder PC; Leiter EH. 2002. Deconstructing and reconstructing obesity-induced diabetes (diabesity) in mice. Diabetes 51(3):825-32PubMed: 11872687 MGI: J:75024
Taylor BA; Wnek C; Schroeder D; Phillips SJ. 2001. Multiple obesity QTLs identified in an intercross between the NZO (New Zealand obese) and the SM (small) mouse strains. Mamm Genome 12(2):95-103PubMed: 11210195 MGI: J:67838
Watkins SM; Reifsnyder PR; Pan HJ; German JB; Leiter EH. 2002. Lipid metabolome-wide effects of the PPARgamma agonist rosiglitazone. J Lipid Res 43(11):1809-17PubMed: 12401879 MGI: J:109849

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Dietary Information
- New Diet as of March 2015: Lab Diet® 5K0Q (6% fat)
Breeding Considerations

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].
- Additional Breeding and Husbandry Support
Mating System
- Sibling x Sibling
Appearance
- albino
  Related Genotype: A/A Tyr^c/Tyr^c
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

AX18 (Maximum)

Pricing & Availability

Available for Pre-order

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Inbred, 1 pair minimum will be supplied

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Notice regarding NONcNZO10/LtJ Female

Notice regarding NONcNZO10/LtJ Male

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org