C3.Cg-Irs1^Sml H2^b/GrsrJ

Stock No:: 001768 |; small

Cryo Recovery

Overview

Also Known As: small

These mice carry a spontaneous mutation at the Irs1 locus characterized by hyperinsulinemia with only mild insulin resistance, a paucity of body fat, deficiencies in bone development and homeostasis, and hearing loss.

Genetic overview

Genetic Background	Generation

Irs1^Sml

Allele Type	Gene Symbol	Gene Name
Spontaneous	Irs1	insulin receptor substrate 1

H2^b

Allele Type	Gene Symbol	Gene Name
Not Applicable	H2	histocompatibility-2, MHC

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Endocrine Deficiency Research
Internal/Organ Research
Developmental Biology Research
Diabetes and Obesity Research
Sensorineural Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The small mutation causes hyperinsulinemia with only mild insulin resistance, a paucity of body fat, deficiencies in bone development and homeostasis, and hearing loss. Homozygotes can be distinguished by 2 weeks of age by their smaller body size and thin short tails, and adult homozygotes are visibly smaller with a tail that is 20% shorter than in wild-type controls. Hearing loss was shown through increased ABR threshold values when assessed between 8 and 12 weeks of age. The skeletal defects include shortened femurs with smaller growth plates, decreased cortical and trabecular thickness and abnormal trabecular number, with an increase in the number of osteoclasts and osteoblasts per bone perimeter but impaired osteoblast proliferation and differentiation in culture. This spontaneous point mutation is semidominant in some aspects of phenotype, unlike targeted mutations of this gene. Heterozygotes are statistically smaller than wild-type controls, but the severity of dwarfing is not readily apparent as it is with homozygotes. Heterozygotes also display an intermediate phenotype for serum insulin, femur length, reduction in femur growth plate size, bone mineral density, leanness, osteoblast function, cortical thickness, periosteal circumference, and mineral apposition rate. There is a variation by gender on the impact on bone structure such that female homozygotes have a decrease in trabecular number while males have an increase but those trabeculae are 34% thinner than normal, and the bone volume is more severely reduced in females than in males. An increase in osteoblasts and osteoclasts in the bone perimeter was found to reach statistical significance in female homozygotes but was less pronounced in male homozygotes. Additionally, in heterozygous females but not males fasting serum insulin like growth factor 1 is reduced to an intermediary level.

Development

The Irs1^sml mutation arose spontaneously on the C3.SW-H2^b/SnJ strain (stock #000438) in the laboratory of Dr. Ed Birkenmeier at The Jackson Laboratory in approximately 1988. This mutation has been maintained via sibling intercrossing heterozygotes with homozygotes. In 2010 this strain reached generation F77.

Selected References

DeMambro VE; Kawai M; Clemens TL; Fulzele K; Maynard JA; Marin de Evsikova C; Johnson KR; Canalis E; Beamer WG; Rosen CJ; Donahue LR. 2010. A novel spontaneous mutation of Irs1 in mice results in hyperinsulinemia, reduced growth, low bone mass and impaired adipogenesis. J Endocrinol 204(3):241-53PubMed: 20032200 MGI: J:163661

View All References

Genetics

Irs1^Sml

Allele Symbol: Irs1^Sml

Allele Name	small
Allele Type	Spontaneous
Allele Synonym(s)	small; Irs1^Sml
Gene Symbol and Name	Irs1, insulin receptor substrate 1
Gene Synonym(s)	IRS-1; G972R; HIRS-1; IRS1IRM
Strain of Origin	C3.SW-H2^b/SnJ
Chromosome	1
Molecular Note	This spontaneous mutation has a deletion of one adenine in exon 1 at position 1559 which results in a frameshift leading to a premature stop codon predicted to yield only a 211 amino acid protein rather than the full-length 1233 amino acids. Western blot analysis using a C-terminus specific antibody failed to detect a protein product in liver extracts of homozygotes.

H2^b

Allele Symbol: H2^b

Allele Name	b variant
Allele Type	Not Applicable
Allele Synonym(s)	H2^b; b variant
Gene Symbol and Name	H2, histocompatibility-2, MHC
Gene Synonym(s)	H-2; MHC-II; H-2
Strain of Origin	Not Applicable
Chromosome	17
General Note	The b variant has been observed in the following strains: C57BL/10, C57BL/10SnJ, BXSB/MpJ, C57BL/6J, C57L/J, LP/J, 129P3/J, 129P1/ReJ.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Genotype: H2^b related

Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers

Genotype: Irs1^Sml related

Endocrine Deficiency Research
- Adipose Defects
- Bone/Bone Marrow Defects
Internal/Organ Research
- Adipose Defects
- Skeleton
  - Bone
Developmental Biology Research
- Growth Defects
  - Growth Defects (homozygous)
- Skeletal Defects
Diabetes and Obesity Research
- Hyperinsulinemia
- Insulin Resistance
Sensorineural Research
- Hearing Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Irs1^Sml/Irs1^Sml
C3.Cg-Irs1 H2/GrsrJ

adipose tissue phenotype

decreased percent body fat/body weight
significantly reduced percent body fat as assessed by whole body DEXA analysis at 16 weeks of age
(MGI Ref ID J:163661)

immune system phenotype

increased osteoclast cell number
an increase in number of both osteoblasts and osteoclasts per bone perimeter in distal femurs is found in both males and females but reaches significance only in females
(MGI Ref ID J:163661)

limbs/digits/tail phenotype

abnormal femur morphology
femur length is shortened, volumetric and areal bone mineral density are reduced, periosteal circumference and cortical thickness are reduced, trabecular number and trabecular thickness are reduced, the mineral apposition rate and bone formation rate are reduced, the minerializing surface per bone surface is less than in controls, there is a reduction in thickness of the growth plate, and there is an increase in the number of osteoclasts and osteoblasts per bone perimeter that reaches significance in females but is only suggested in males
(MGI Ref ID J:163661)
les but is only suggested in males
(MGI Ref ID J:163661)
reduced, the minerializing surface per bone surface is less than in controls, there is a reduction in thickness of the growth plate, and there is an increase in the number of osteoclasts and osteoblasts per bone perimeter that reaches significance in fema
(MGI Ref ID J:163661)

abnormal tail morphology
by 2 weeks of age the tail is thin and short compared with that of controls and after weaning the tail continues to have a 20% reduction in length compared with controls
(MGI Ref ID J:163661)

short femur
(MGI Ref ID J:163661)

short tail
(MGI Ref ID J:163661)

thin tail
(MGI Ref ID J:163661)

cellular phenotype

decreased osteoblast proliferation
in culture osteoblasts have impaired proliferation and differentiation
(MGI Ref ID J:163661)

impaired osteoblast differentiation
in culture osteoblasts have impaired proliferation and differentiation
(MGI Ref ID J:163661)

skeleton phenotype

abnormal bone mineralization
(MGI Ref ID J:163661)

abnormal bone structure
(MGI Ref ID J:163661)

abnormal femur morphology
femur length is shortened, volumetric and areal bone mineral density are reduced, periosteal circumference and cortical thickness are reduced, trabecular number and trabecular thickness are reduced, the mineral apposition rate and bone formation rate are reduced, the minerializing surface per bone surface is less than in controls, there is a reduction in thickness of the growth plate, and there is an increase in the number of osteoclasts and osteoblasts per bone perimeter that reaches significance in females but is only suggested in males
(MGI Ref ID J:163661)
les but is only suggested in males
(MGI Ref ID J:163661)
reduced, the minerializing surface per bone surface is less than in controls, there is a reduction in thickness of the growth plate, and there is an increase in the number of osteoclasts and osteoblasts per bone perimeter that reaches significance in fema
(MGI Ref ID J:163661)

decreased bone mineral density
(MGI Ref ID J:163661)

decreased long bone epiphyseal plate size
the growth plate of the proximal femur is markedly reduced in thickness
(MGI Ref ID J:163661)

decreased osteoblast proliferation
in culture osteoblasts have impaired proliferation and differentiation
(MGI Ref ID J:163661)

decreased trabecular bone thickness
reduction in bone volume per total volume, trabecular thickness, and trabecular number is significant in both males and females but more severe in females
(MGI Ref ID J:163661)

impaired osteoblast differentiation
in culture osteoblasts have impaired proliferation and differentiation
(MGI Ref ID J:163661)

increased osteoblast cell number
an increase in number of both osteoblasts and osteoclasts per bone perimeter in distal femurs is found in both males and females but reaches significance only in females
(MGI Ref ID J:163661)

increased osteoclast cell number
an increase in number of both osteoblasts and osteoclasts per bone perimeter in distal femurs is found in both males and females but reaches significance only in females
(MGI Ref ID J:163661)

short femur
(MGI Ref ID J:163661)

growth/size/body region phenotype

decreased body size
by 2 weeks of age homozygotes are distinctly smaller and after weaning they are approximately 60% of the size by weight of heterozygotes and less than half the size by weight of wildtype controls
(MGI Ref ID J:163661)

decreased body weight
(MGI Ref ID J:163661)

proportional dwarf
(MGI Ref ID J:163661)

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
although no inner ear defects are evident, the ABR thresholds at 8, 16, and 32 kHz are significantly elevated in both male and female homozygotes assessed between 8 and 12 weeks of age
(MGI Ref ID J:163661)

hematopoietic system phenotype

increased osteoclast cell number
an increase in number of both osteoblasts and osteoclasts per bone perimeter in distal femurs is found in both males and females but reaches significance only in females
(MGI Ref ID J:163661)

homeostasis/metabolism phenotype

decreased circulating glucose level
fasting glucose levels are 30-40% lower than those of wild-type controls
(MGI Ref ID J:163661)

impaired glucose tolerance
when challenged with glucose after an overnight fast at 8 weeks of age the serum glucose levels rise as expected initially with normal kinetics but remain lower than those of wild-type controls
(MGI Ref ID J:163661)

increased circulating insulin level
homozygotes have 3.5 to 4-fold higher circulating insulin levels and a modest increase in insulin-like growth factor 1 under fasting conditions than wild-type controls
(MGI Ref ID J:163661)

insulin resistance
mild insulin resistance is revealed in non-fasting insulin tolerance tests whereing glucose levels decrease but not to the full extent seen in wild-type controls
(MGI Ref ID J:163661)

Genotype: Irs1^Sml/Irs1⁺
C3.Cg-Irs1 H2/GrsrJ

adipose tissue phenotype

decreased total body fat amount
heterozygotes have less fat than wild-type controls but more than homozygotes
(MGI Ref ID J:163661)

growth/size/body region phenotype

decreased body weight
reduction in body weight relative to wild-type controls but less severe than in homozygotes
(MGI Ref ID J:163661)

homeostasis/metabolism phenotype

increased circulating insulin level
both male and female heterozygotes have an increase in fasted serum insulin that is intermediary between homozygotes and wild-type controls, and female heterozygotes, but not males, have decreased fasting serum insulin-like growth factor 1
(MGI Ref ID J:163661)

limbs/digits/tail phenotype

abnormal femur morphology
heterozygotes have a less severe phenotype than homozygotes with slight reduction in periosteal circumference, cortical thickness, trabecular thickness, size of the growth plate, and femur length
(MGI Ref ID J:163661)

short femur
slightly shorter than in wild-type controls but not shortened to the degree found in homozygotes
(MGI Ref ID J:163661)

skeleton phenotype

abnormal femur morphology
heterozygotes have a less severe phenotype than homozygotes with slight reduction in periosteal circumference, cortical thickness, trabecular thickness, size of the growth plate, and femur length
(MGI Ref ID J:163661)

decreased bone mineral density
intermediate phenotype between homozygotes and wild-type controls
(MGI Ref ID J:163661)

decreased long bone epiphyseal plate size
the growth plate in the proximal femur is mildly reduced in size compared with wild-type controls, but not to the degree found in homozygotes
(MGI Ref ID J:163661)

short femur
slightly shorter than in wild-type controls but not shortened to the degree found in homozygotes
(MGI Ref ID J:163661)

References

DeMambro VE; Kawai M; Clemens TL; Fulzele K; Maynard JA; Marin de Evsikova C; Johnson KR; Canalis E; Beamer WG; Rosen CJ; Donahue LR. 2010. A novel spontaneous mutation of Irs1 in mice results in hyperinsulinemia, reduced growth, low bone mass and impaired adipogenesis. J Endocrinol 204(3):241-53PubMed: 20032200 MGI: J:163661

Additional - H2^b related
Additional - Irs1^Sml related

Technical Support

Contact Technical Support

Genotyping Protocols

Genotyping resources and troubleshooting

Citation
When using the small mouse strain in a publication, please cite the originating article(s) and include JAX stock #001768 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

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Live Mouse

Age Genotype Price

weeks

Cryorecovery - Pricing

Service Genotype Price

Heterozygous for Irs1<Sml> H2

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

Related Products and Services

Frozen Mouse Embryo C3.Cg-Irs1<Sml> H2/GrsrJ $2595.00
Frozen Mouse Embryo C3.Cg-Irs1<Sml> H2/GrsrJ $2595.00
Frozen Mouse Embryo C3.Cg-Irs1<Sml> H2/GrsrJ $3373.50
Frozen Mouse Embryo C3.Cg-Irs1<Sml> H2/GrsrJ $3373.50

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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.

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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.

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Frozen Mouse Embryo	C3.Cg-Irs1<Sml> H2<b>/GrsrJ	$2595.00
Frozen Mouse Embryo	C3.Cg-Irs1<Sml> H2<b>/GrsrJ	$2595.00
Frozen Mouse Embryo	C3.Cg-Irs1<Sml> H2<b>/GrsrJ	$3373.50
Frozen Mouse Embryo	C3.Cg-Irs1<Sml> H2<b>/GrsrJ	$3373.50

Also Known As: small

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Irs1Sml

Allele Symbol: Irs1Sml

H2b

Allele Symbol: H2b

Disease Terms

Research Areas By Genotype

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

Genotype: H2b related

Genotype: Irs1Sml related

Mammalian Phenotype Terms by Genotype

Genotype: Irs1Sml/Irs1SmlC3.Cg-Irs1 H2/GrsrJ

adipose tissue phenotype

immune system phenotype

limbs/digits/tail phenotype

cellular phenotype

skeleton phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

Genotype: Irs1Sml/Irs1+C3.Cg-Irs1 H2/GrsrJ

adipose tissue phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

limbs/digits/tail phenotype

skeleton phenotype

References

Additional - H2b related

Additional - Irs1Sml related

Genotyping Protocols

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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Irs1^Sml

Allele Symbol: Irs1^Sml

H2^b

Allele Symbol: H2^b

Genotype: H2^b related

Genotype: Irs1^Sml related

Genotype: Irs1^Sml/Irs1^Sml
C3.Cg-Irs1 H2/GrsrJ

Genotype: Irs1^Sml/Irs1⁺
C3.Cg-Irs1 H2/GrsrJ

Additional - H2^b related

Additional - Irs1^Sml related