Overview

Also Known As:IRS-4 KO

These Irs4 knock-out mice exhibit impaired glucose tolerance and slight retardation in growth rate.

Donating Investigator

Gustav E. Lienhard, Dartmouth Medical School

Genetic overview

Genetic Background	Generation

Irs4^tm1Lhd

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Irs4	insulin receptor substrate 4

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Research Applications

Diabetes and Obesity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Irs4^tm1Lhd targeted mutation are viable and fertile. However, homozygous mutant mice do appear to be at a greater risk of perinatal lethality and tend to produce fewer litters. At birth, surviving mice appear normal in size and do not display any gross physical or behavioral abnormalities. RT-PCR fails to detect Irs4 mRNA in any tissues analyzed. Growth rate appears to be slightly retarded beginning 6 weeks of age (males about 10% lighter). Homozygotes also exhibit impaired glucose tolerance, and have slightly lower blood glucose levels when compared to wildtype mice. These phenotypes are more pronounced in males than in females.

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 single Irs4 exon. 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 mice were bred to C57BL/6 females. Offspring animals were bred to homozygosity.

Control Suggestions

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Fantin VR; Wang Q; Lienhard GE; Keller SR. 2000. Mice lacking insulin receptor substrate 4 exhibit mild defects in growth, reproduction, and glucose homeostasis. Am J Physiol Endocrinol Metab 278(1):E127-33PubMed: 10644546 MGI: J:59964

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Genetics

Irs4^tm1Lhd

Allele Symbol: Irs4^tm1Lhd

Allele Name	targeted mutation 1, Gustav E Lienhard
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Irs4-; IRS-4 null
Gene Symbol and Name	Irs4, insulin receptor substrate 4
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	X
Molecular Note	A neomycin resistance cassette replaced the entire coding sequence of the gene except for 457 bp at the 3' end. Reverse transcription-PCR detected no mRNA expression in brain, skeletal muscle, kidney, or liver of homozygous mutant mice.
Mutations Made By	Gustav Lienhard, Dartmouth Medical School

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Irs4^tm1Lhd related

Diabetes and Obesity Research
- Insulin Receptors and Growth Factors

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Irs4^tm1Lhd/Y
involves: 129S4/SvJae * BALB/c

homeostasis/metabolism phenotype

impaired glucose tolerance
- at 6-10 weeks, male hemizygotes show an impaired tolerance that is statistically significant at the 60, 90, and 120 min time points of the oral glucose tolerance test

reproductive system phenotype

decreased litter size
- pairs of mutant mice produce an average of 2.0 ¿ 0.5 litters per pair (range 0-3), whereas wild-type mice produce an average of 3.1 ¿ 0.1 litters per pair (range 3-4)
- ~50% of mutant litters die within a few days of birth relative to only 8% of wild-type litters
- the average sizes of surviving litters are almost the same for mutant and wild-type mice

abnormal fertility/fecundity
- male hemizygotes exhibit reduced ability to produce live offspring when mated with homozygous mutant females

Genotype: Irs4^tm1Lhd/Irs4^tm1Lhd
involves: 129S4/SvJae * BALB/c

reproductive system phenotype

decreased litter size
- pairs of mutant mice produce an average of 2.0 ¿ 0.5 litters per pair (range 0-3), whereas wild-type mice produce an average of 3.1 ¿ 0.1 litters per pair (range 3-4)
- ~50% of mutant litters die within a few days of birth relative to only 8% of wild-type litters
- the average sizes of surviving litters are almost the same for mutant and wild-type mice

abnormal fertility/fecundity
- female homozygotes exhibit reduced ability to produce live offspring when mated with hemizygous mutant males

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

Genotype: Irs4^tm1Lhd/Irs4^tm1Lhd
involves: 129S4/SvJae * C57BL/6

behavior/neurological phenotype

abnormal maternal nurturing
- female homozygotes may be less nurturing of their pups than wild-type females, as suggested by an observed decrease in the number of surviving litters

homeostasis/metabolism phenotype

abnormal glucose tolerance
- at 6 months, older female homozygotes exhibit only a very slightly impaired glucose tolerance, which is statistically significant at 10 min but not at other time points

mammalian phenotype

growth/size/body region phenotype
- Normal - female homozygotes exhibit a very slight reduction in body size relative to wild-type mice; however, this difference does not reach statistical significance

homeostasis/metabolism phenotype
- Normal - female homozygotes show slightly reduced blood glucose levels in both the fasted and fed states at 6-10 weeks, and in the fed state at 6 months; however, none of these differences reach statistical significance
- Normal - in addition, plasma insulin levels remain unaffected in the fed and fasted state at both ages

reproductive system phenotype

decreased litter size
- the average size of surviving litters from mutant mice is slightly reduced relative to wild-type litters
- 36% of mutant litters die within a few days of birth relative to only 5% of wild-type litters
- pairs of mutant mice produce an average of 1.8 ¿ 0.4 litters per pair (range 0-3 litters) over a 3-month period, whereas wild-type mice produce an average of 2.9 ¿ 0.1 litters per pair (range 2-3 litters)

abnormal fertility/fecundity
- female homozygotes exhibit reduced ability to produce live offspring when mated with hemizygous mutant males

Genotype: Irs4^tm1Lhd/Y
involves: 129S4/SvJae * C57BL/6

growth/size/body region phenotype

postnatal growth retardation
- male hemizygotes exhibit a growth retardation beyond 6 weeks of age

decreased body weight
- at 9 weeks and beyond, the weight of male hemizygotes is ~10% less that of wild-type mice

homeostasis/metabolism phenotype

impaired glucose tolerance
- at 6-10 weeks, male hemizygotes show a slightly impaired glucose tolerance, with significant differences noted at the 90 and 120 min time points
- at 6 months, significant differences are only noted at the 20 min point of the oral glucose tolerance test

decreased circulating glucose level
- at 6-10 weeks, male hemizygotes exhibit a slight but significant reduction in blood glucose levels in both the fasted and fed states; however, these differences become statistically insignificant at 6 months
- in contrast, plasma insulin levels remain unaffected in the fed and fasted state at both ages

reproductive system phenotype

abnormal fertility/fecundity
- male hemizygotes exhibit reduced ability to produce live offspring when mated with homozygous mutant females

decreased litter size
- the average size of surviving litters from mutant mice is slightly reduced relative to wild-type litters
- pairs of mutant mice produce an average of 1.8 ¿ 0.4 litters per pair (range 0-3 litters) over a 3-month period, whereas wild-type mice produce an average of 2.9 ¿ 0.1 litters per pair (range 2-3 litters)
- 36% of mutant litters die within a few days of birth relative to only 5% of wild-type litters

References

Fantin VR; Wang Q; Lienhard GE; Keller SR. 2000. Mice lacking insulin receptor substrate 4 exhibit mild defects in growth, reproduction, and glucose homeostasis. Am J Physiol Endocrinol Metab 278(1):E127-33PubMed: 10644546 MGI: J:59964

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):3213-22PubMed: 12502742 MGI: J:80976

Additional - Irs4^tm1Lhd related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

This strain arose on a B6;129 background and is maintained on the same. Coat color expected from breeding:Black.
- Additional Breeding and Husbandry Support
Citation
When using the IRS-4 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003901 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	X linked - Heterozygous Females and Wild-type Males for Irs4<tm1Lhd>, 1 pair minimum

Related Products and Services

Frozen Mouse Embryo	B6;129-Irs4<tm1Lhd>/J	$2595.00
Frozen Mouse Embryo	B6;129-Irs4<tm1Lhd>/J	$2595.00
Frozen Mouse Embryo	B6;129-Irs4<tm1Lhd>/J	$3373.50
Frozen Mouse Embryo	B6;129-Irs4<tm1Lhd>/J	$3373.50

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

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:IRS-4 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Irs4tm1Lhd

Allele Symbol: Irs4tm1Lhd

Disease Terms

Research Areas By Phenotype

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

Genotype: Irs4tm1Lhd related

Mammalian Phenotype Terms by Genotype

Genotype: Irs4tm1Lhd/Yinvolves: 129S4/SvJae * BALB/c

homeostasis/metabolism phenotype

reproductive system phenotype

Genotype: Irs4tm1Lhd/Irs4tm1Lhdinvolves: 129S4/SvJae * BALB/c

reproductive system phenotype

Genotype: Irs4tm1Lhd/Irs4tm1Lhdinvolves: 129S4/SvJae * C57BL/6

behavior/neurological phenotype

homeostasis/metabolism phenotype

mammalian phenotype

reproductive system phenotype

Genotype: Irs4tm1Lhd/Yinvolves: 129S4/SvJae * C57BL/6

growth/size/body region phenotype

homeostasis/metabolism phenotype

reproductive system phenotype

References

Additional References

Additional - Irs4tm1Lhd related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Irs4^tm1Lhd

Allele Symbol: Irs4^tm1Lhd

Genotype: Irs4^tm1Lhd related

Genotype: Irs4^tm1Lhd/Y
involves: 129S4/SvJae * BALB/c

Genotype: Irs4^tm1Lhd/Irs4^tm1Lhd
involves: 129S4/SvJae * BALB/c

Genotype: Irs4^tm1Lhd/Irs4^tm1Lhd
involves: 129S4/SvJae * C57BL/6

Genotype: Irs4^tm1Lhd/Y
involves: 129S4/SvJae * C57BL/6

Additional - Irs4^tm1Lhd related