Overview

Also Known As:New Zealand Obese

NZO inbred mice and strains derived from them develop severe obesity, and are thus useful for studying obesity and Type 2 diabetes.

Genetic overview

Genetic Background	Generation
	?+F69 (2020-01-20 00:00:00)

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Research Applications

Diabetes and Obesity Research
Reproductive Biology Research

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Base Price

Starting at:

$230.00 Domestic price for female 4-week

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Details

Detailed 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.

Selected References

Petkov PM; Cassell MA; Sargent EE; Donnelly CJ; Robinson P; Crew V; Asquith S; Haar RV; Wiles MV. 2004. Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse. Genomics 83(5):902-11PubMed: 15081119 MGI: J:89298
Timmermans S; Van Montagu M; Libert C. 2017. Complete overview of protein-inactivating sequence variations in 36 sequenced mouse inbred strains. Proc Natl Acad Sci U S A 114(34):9158-9163PubMed: 28784771 MGI: J:244295

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Genetics

Pctp^R120H

Allele Symbol: Pctp^R120H

Allele Name	R120H
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	Pctp, phosphatidylcholine transfer protein
Gene Synonym(s)
Strain of Origin	NZO
Chromosome	11
Molecular Note	A G-to-A transition in exon 4 resulted in the arginine to histidine substitution at amino acid 120 (p.R120H) in NZO, NZB/BINJ and NZW/LacJ strains. This mutation renders the protein inactive.

Cox7a2l^l

Allele Symbol: Cox7a2l^l

Allele Name	long
Allele Type	Not Applicable (Not Specified)
Allele Synonym(s)	SCAF1¹¹³
Gene Symbol and Name	Cox7a2l, cytochrome c oxidase subunit 7A2 like
Gene Synonym(s)
Strain of Origin	multiple strains
Chromosome	17
General Note	Querying the sequences of the Sanger Mouse Genomes Project reveals that the short allele with its 6 bp deletion exists in C57BL/6J, C57BL/10J, C57BL/6NJ, C58/J, BALB/cJ, C3H/HeH, 129S5/SvEvBrd, NZW/LacZ, and SEA/GnJ, but the long allele lacking the deletion exists in 129S1/SvImJ, A/J, AKR/J, BTBR T⁺ Itpr3^tf/J, BUB/BnJ, C3H/HeJ, C57BR/cdJ, C57L/J, CAST/EiJ, CBA/J, DBA/1J, DBA/2J, FVB/NJ, I/LnJ, KK/HiJ, LEWES/EiJ, LP/J, MOLF/EiJ, NOD/ShiLtJ, NZB/BlNJ, NZO/HlLtJ, PWK/PhJ, RF/J, SPRET/EiJ, ST/bJ, WSB/EiJ, ZALENDE/EiJ.
Molecular Note	This allele encodes the long isoform with 113 amino acids. It is found in 129S2/SvPasCrl, CBA/CaOlaHsd, Hsd:ICR, and NZB/OlaHsd.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Diabetes and Obesity Research
- Hyperinsulinemia
  - males
- Insulin Resistance
  - males
- Type 2 Diabetes (NIDDM)
  - males
- Obesity With Diabetes
  - severe
- Hyperglycemia
  - males
Reproductive Biology Research
- Fertility Defects
- Gonadal Tumors
  - granulosa cell tumors

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Pctp^R120H/Pctp⁺
NZO

homeostasis/metabolism phenotype

abnormal lipid homeostasis
- phosphatidlycholine transfer activity is essentially absent in mutants
- this mutation abolishes the activity of phosphatidlycholine transfer protein

Phenotype Information

Festing Inbred Strain Characteristics: NZO

References

Petkov PM; Cassell MA; Sargent EE; Donnelly CJ; Robinson P; Crew V; Asquith S; Haar RV; Wiles MV. 2004. Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse. Genomics 83(5):902-11PubMed: 15081119 MGI: J:89298
Timmermans S; Van Montagu M; Libert C. 2017. Complete overview of protein-inactivating sequence variations in 36 sequenced mouse inbred strains. Proc Natl Acad Sci U S A 114(34):9158-9163PubMed: 28784771 MGI: J:244295

Additional References

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):567-70PubMed: 4115740 MGI: 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):833-42PubMed: 12118085 MGI: J:77828
Keane TM; Goodstadt L; Danecek P; White MA; Wong K; Yalcin B; Heger A; Agam A; Slater G; Goodson M; Furlotte NA; Eskin E; Nellaker C; Whitley H; Cleak J; Janowitz D; Hernandez-Pliego P; Edwards A; Belgard TG; Oliver PL; McIntyre RE; Bhomra A; Nicod J; Gan X; Yuan W; van der Weyden L; Steward CA; Bala S; Stalker J; Mott R; Durbin R; Jackson IJ; Czechanski A; Guerra-Assuncao JA; Donahue LR; Reinholdt LG; Payseur BA; Ponting CP; Birney E; Flint J; Adams DJ. 2011. Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477(7364):289-94PubMed: 21921910 MGI: J:177037
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

Additional - Cox7a2l^l related

Additional - Pctp^R120H related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K54 formulation (4% fat)
Breeding Considerations

This inbred strain is a challenging breeder (can have a high rate of non-productive matings).
- Additional Breeding and Husbandry Support
Mating System
- Sibling x Sibling
Appearance
- agouti
  Related Genotype: A/A
Citation
When using the New Zealand Obese mouse strain in a publication, please include JAX stock #002105 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX12 (Maximum)

Pricing & Availability

Available Now

Domestic
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous, 1 pair minimum

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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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