Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N1   Donating Investigator Gustav Lienhard,   Dartmouth Medical School

Description
Mice that are homozygous null for the Irs3 gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The inactivation of Irs3 appears not to perturb glucose homeostasis with the possible exception of young (9-13 weeks, postnatal) homozygous males. These mice exhibit a fasting plasma insulin level 60% that of wildtype controls. The difference is not observed in female or older (6 months) homozygous null mice.

Development
A targeting vector containing a herpes simplex virus thymidine kinase gene and a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt the Irs3 coding region sequence. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male was bred to C57BL/6 females. Offspring animals were bred to homozygosity.

Control Information

	Control
	101045 B6129SF2/J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Irs3^tm1Lhd/Irs3^tm1Lhd

        involves: 129S4/SvJae * C57BL/6

• normal phenotype
• no abnormal phenotype detected (MGI Ref ID J:55667)
  • in general, homozygotes are viable, fertile and display normal growth and development as well as normal glucose homeostasis and normal insulin-stimulated glucose transport in adipocytes
  • at 9-13 weeks of age, young male homozygotes show fasting plasma insulin levels that are 60% of wild-type levels; however, this difference is no longer apparent at 6 months

Genes & Alleles

Gene & Allele Information

Allele Symbol		Irs3tm1Lhd
Allele Name		targeted mutation 1, Gustav E Lienhard
Allele Type		Targeted (knock-out)
Common Name(s)		IRS-3-/-; IRS3-;
Mutation Made By		Gustav Lienhard,   Dartmouth Medical School
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Irs3, insulin receptor substrate 3
Chromosome		5
Gene Common Name(s)		AA408304; expressed sequence AA408304;
Molecular Note		A neomycin resistance cassette disrupted the coding region of the gene. [MGI Ref ID J:55667]

Genotyping

Genotyping Information

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

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Liu SC; Wang Q; Lienhard GE; Keller SR. 1999. Insulin receptor substrate 3 is not essential for growth or glucose homeostasis. J Biol Chem 274(25):18093-9. [PubMed: 10364263]  [MGI Ref ID J:55667]

Additional References

Laustsen PG; Michael MD; Crute BE; Cohen SE; Ueki K; Kulkarni RN; Keller SR; Lienhard GE; Kahn CR. 2002. Lipoatrophic diabetes in Irs1(-/-)/Irs3(-/-) double knockout mice. Genes Dev 16(24):3213-22. [PubMed: 12502742]  [MGI Ref ID J:80976]

Terauchi Y; Matsui J; Suzuki R; Kubota N; Komeda K; Aizawa S; Eto K; Kimura S; Nagai R; Tobe K; Lienhard GE; Kadowaki T. 2003. Impact of genetic background and ablation of insulin receptor substrate (IRS)-3 on IRS-2 knock-out mice. J Biol Chem 278(16):14284-90. [PubMed: 12493745]  [MGI Ref ID J:82924]

Irs3^tm1Lhd related

Laustsen PG; Michael MD; Crute BE; Cohen SE; Ueki K; Kulkarni RN; Keller SR; Lienhard GE; Kahn CR. 2002. Lipoatrophic diabetes in Irs1(-/-)/Irs3(-/-) double knockout mice. Genes Dev 16(24):3213-22. [PubMed: 12502742]  [MGI Ref ID J:80976]

North TE; de Bruijn MF; Stacy T; Talebian L; Lind E; Robin C; Binder M; Dzierzak E; Speck NA. 2002. Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity 16(5):661-72. [PubMed: 12049718]  [MGI Ref ID J:76800]

Terauchi Y; Matsui J; Suzuki R; Kubota N; Komeda K; Aizawa S; Eto K; Kimura S; Nagai R; Tobe K; Lienhard GE; Kadowaki T. 2003. Impact of genetic background and ablation of insulin receptor substrate (IRS)-3 on IRS-2 knock-out mice. J Biol Chem 278(16):14284-90. [PubMed: 12493745]  [MGI Ref ID J:82924]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two animals carrying the mutation of interest will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location). This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	101045 B6129SF2/J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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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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