Description

Strain Information

Former Names NZO/HILtJ    (Changed: 24-OCT-07 ) NZO/HlJ    (Changed: 15-DEC-04 ) Type Inbred Strain; Additional information on Inbred Strains. Mating System Sibling x Sibling         (Female x Male) Species laboratory mouse H2 Haplotype z Generation ?+F39 (05-DEC-07)

Appearance
agouti
Related Genotype: A/A

Description
NZO mice of both sexes exhibit high birth weights and are significantly heavier at weaning age, Severe obesity (including both visceral and subcuatneous fat depots) develops even when mice are maintained on a standard diet containing 4.5% fat. Both males and females of the NZO/Hl substrain exhibit impaired glucose tolerance (IGT), but subsequent type 2 maturity onset (NIDDM) diabetes development is limited to males, with a phenotype penetrance of 50% or less. NZO/Hl mice also show anti-insulin receptor antibodies, a defect in leptin transport, and hypertension. The genetic lesion appears to be within the islets of Langerhans as transfer of pancreatic islets from normal mice returns body weights and blood glucose levels to within normal range. Ovarian granulosa cell tumors, lymphomas, duodenal, and lung tumors have also been noted to occur in NZO mice at an elevated frequency. F1 hybrids of NON/ShiLt and NZO/Hl provide a new model of obesity-induced diabetes. Male (NON/ShiLt x NZO/Hl)F1 hybrids are obese (BW = 53.5 g by 16 weeks) and almost all develop maturity onset NIDDM. F1 males on a 4% diet will develop hyperglycemia around 20 to 24 weeks of age; increasing the fat content of the diet accelerates diabetes onset to 16 to 20 weeks of age. (NZO/Hl x NON/ShiLt)F1 hybrids will develop diabetes slightly faster than their reciprocal cross due to the NZO maternal environment; however this cross is difficult to produce due to the inherently poor breeding performance of NZO/HlJ female mice. F1 females exhibit a weight gain similar to the NZO parent, and have impaired glucose tolerance but are resistant to diabetes development. Diabetes development can be accelerated to eight to 12 weeks by fostering onto an F1 dam. Reciprocal backcrosses to the parental strains and analysis of (NON/ShiLt x NZO/Hl)F2 mice has led to the identification of a number of complex diabetes-predisposing ("diabesity") QTLs. Dr. Leiter's research group at The Jackson Laboratory is currently developing a series of nine recombinant congenic strains (RCS) made by backcrossing the (NZO/Hl x NON/ShiLt)F1 for two generations onto the NON/ShiLt background before inbreeding (~12% NZO/Hl, 88% NON/ShiLt genomes). Preliminary analysis indicates that body weight gains of all RCS are higher than NON/ShiLt, but none are as obese as NZO/Hl; some of these RCS develop NIDDM while others are resistant. These new strains will be useful to further analyze diabesity QTLs and as new models for type 2 (NIDDM) diabetes. An additional benefit of the RCS is better breeding performance than NZO/Hl.

Development
The New Zealand Obese (NZO) inbred mouse strain was initially selected for polygenic obesity. NZO mice share a common origin with New Zealand Black mice (NZB). M. Bielschowsky began inbreeding of outbred mice obtained from the Imp. Cancer Research Fund, London began at the University of Otago Medical School in 1948.

Related Strains

Strains carrying   Pctp^R120H allele

000684	NZB/BlNJ
001058	NZW/LacJ

View Strains carrying   Pctp^R120H     (2 strains)

Strains carrying other alleles of Pctp

006607

B6.129-Pctptm1Bor/J

View Strains carrying other alleles of Pctp     (1 strain)

Additional Web Information

Genetic Quality Control Annual Report
JAX^® NOTES, Fall 2002; 487. New Polygenic Obesity Mouse Models.
JAX^® NOTES, Winter 2006; 504. JAX^® Mice Strain Sleeps While Standing.

Phenotype

Phenotype Information

View Phenotypic Data

Phenotypic Data

Mouse Phenome Database
Festing Inbred Strain Characteristics: NZO

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Pctp^R120H/Pctp⁺

        NZO

• homeostasis/metabolism phenotype
• abnormal lipid homeostasis (MGI Ref ID J:114974)
  • this mutation abolishes the activity of phosphatidlycholine transfer protein
  • phosphatidlycholine transfer activity is essentially absent in mutants

View Research Applications

Research Applications

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

Diabetes and Obesity Research
Hyperglycemia (males)
Hyperinsulinemia (males)
Insulin Resistance (males)
Obesity With Diabetes (severe)
Type 2 Diabetes (NIDDM) (males)

Reproductive Biology Research
Fertility Defects
Gonadal Tumors (granulosa cell tumors)

Genes & Alleles

Gene & Allele Information

Allele Symbol		PctpR120H
Allele Name		R120H
Allele Type		Spontaneous
Strain of Origin		NZO
Gene Symbol and Name		Pctp, phosphatidylcholine transfer protein
Chromosome		11
Gene Common Name(s)		PC-TP; STARD2;
Molecular Note		A G to A transition in exon 4 resulted in the arginine to histidine substitution at amino acid 120 in NZO, NZB/BINJ and NZW/LacJ strains. This mutation rendered the protein was inactive. [MGI Ref ID J:114974]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Bielschowsky M; Goodall CM. 1970. Origin of inbred NZ mouse strains. Cancer Res 30(3):834-6. [PubMed: 5425297]  [MGI Ref ID J:25459]

Gates RJ; Hunt MI; Smith R; Lazarus NR. 1972. Return to normal of blood-glucose, plasma-insulin, and weight gain in New Zealand obese mice after implantation of islets of Langerhans. Lancet 2(777):567-70. [PubMed: 4115740]  [MGI Ref ID J:35290]

Haskell BD; Flurkey K; Duffy TM; Sargent EE; Leiter EH. 2002. The diabetes-prone NZO/HlLt strain. I. Immunophenotypic comparison to the related NZB/BlNJ and NZW/LacJ strains. Lab Invest 82(7):833-42. [PubMed: 12118085]  [MGI Ref ID J:77828]

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):1287-95. [PubMed: 9703330]  [MGI Ref ID J:48957]

Rappaport H; Bielschowsky M; D'Ath EF; Goodall CM. 1971. Malignant lymphomas arising in Peyer's patches and other organs of untreated NZO-Bl mice. Cancer Res 31(12):2047-53. [PubMed: 4941087]  [MGI Ref ID J:25462]

Pctp^R120H related

Pan HJ; Agate DS; King BL; Wu MK; Roderick SL; Leiter EH; Cohen DE. 2006. A polymorphism in New Zealand inbred mouse strains that inactivates phosphatidylcholine transfer protein. FEBS Lett 580(25):5953-8. [PubMed: 17046758]  [MGI Ref ID J:114974]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Mating System	Sibling x Sibling         (Female x Male)
Diet Information	LabDiet® 5K54

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

 

This strain is currently This strain is currently on HOLD - Contact Customer Service for more information..
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development and On Hold

Pricing

Supply Details

Standard Supply	This strain is currently on HOLD - Contact Customer Service for more information.
Supply Notes	Usually shipped between four and six weeks of age. This strain is included in the Mouse Mutant Resource collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

General Terms and Conditions

See Terms of Use

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.

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