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.
Read More +Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Not Applicable | H2 | histocompatibility-2, MHC |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous | Irs1 | insulin receptor substrate 1 |
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.
The Irs1sml mutation arose spontaneously on the C3.SW-H2b/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.
Allele Name | b variant |
---|---|
Allele Type | Not Applicable |
Allele Synonym(s) | |
Gene Symbol and Name | H2, histocompatibility-2, MHC |
Gene Synonym(s) | |
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. |
Allele Name | small |
---|---|
Allele Type | Spontaneous |
Allele Synonym(s) | Irs1sml |
Gene Symbol and Name | Irs1, insulin receptor substrate 1 |
Gene Synonym(s) | |
Strain of Origin | C3.SW-H2b/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. |
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Irs1<Sml> H2<b> |
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 |
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 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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.