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Strain Name:

B6;129S6-Insig1tm1Mbjg Insig2tm1Mbjg/J

Stock Number:

005939

Availability:

Repository- Live

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Additional Licensing and Use Restrictions

Strain Common Names      Insig1f/f Insig2-/-;
Genes & Alleles   Insig1;   Insig1tm1Mbjg;   Insig2;   Insig2tm1Mbjg;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Targeted Mutation
Mating SystemSee Colony Maintenance         (Female x Male)
Specieslaboratory mouse
Donating Investigator Guosheng Liang,   UT Southwestern Medical Center at Dallas
Generation?+F2 (19-DEC-07)

Strain Description
Mice homozygous for both targeted mutations are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This double mutant has normal expression of Insig1 and no Insig2 gene expression or protein in liver. As the Insig1 mutant locus contains a loxP, frt-flanked exon 1, Cre-mediated deletion of exon 1 (encoding amino acids 1-113) terminates gene function. Double homozygous mutant mice die in utero some time after embryonic day 18.5. These mice may be useful in studies of cholesterol synthesis and feedback suppression, sterol regulatory element-binding protein (SREBP) processing pathways, liver metabolism and storage functions, and may have use in insulin-related topics such as diabetes and endocrine/exocrine function.

Strain Development
A targeting vector was designed to insert a loxP, frt-flanked PGK-Neo cassette 2.3-kb upstream of the initiator start codon of the Insig1 exon 1 and insert a third loxP site within the Insig1 intron 1. The Insig2 gene was disrupted by replacement of exons 2 and 3 (encoding amino acids 1-123) with a Neo cassette. The constructs were independently injected into 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric males were bred with C57BL/6NCrl females. Mutant offspring were crossed to create homozygous mouse lines. Mice homozygous for the loxP, frt-flanked exon 1 mutation (Insig1f/f) were bred with Insig2-/- mice to produce mice on a mixed B6;129S6 background homozygous for both targeted mutations.

Gene & Allele Details

Allele Symbol Insig1tm1Mbjg
Allele Name targeted mutation 1, Joseph L Goldstein
Common Name(s) Insig1f; Insig1tm1Jlg;
Strain of Origin129S6/SvEvTac
ES Cell Line NameSM1
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Insig1, insulin induced gene 1
Chromosome 5
Gene Common Name(s) 1810013C12Rik; CL-6; Insig-1; MGC1405; RIKEN cDNA 1810013C12 gene;
Molecular Note A vector was designed to flank exon 1, containing the ATG, with loxP sites. An FRT and floxed neo was inserted upstream of the exon. Transcript was reduced by 20%, possibly due to transcriptional interference from the neo cassette. [MGI Ref ID J:101203]
 
Allele Symbol Insig2tm1Mbjg
Allele Name targeted mutation 1, Joseph L Goldstein
Common Name(s) Insig-2-; Insig2-; Insig2tm1Jlg;
Strain of Origin129S6/SvEvTac
ES Cell Line NameSM1
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Insig2, insulin induced gene 2
Chromosome 1
Gene Common Name(s) 2900053I11Rik; C730043J18Rik; Insig-2; MGC26273; RIKEN cDNA 2900053I11 gene; RIKEN cDNA C730043J18 gene;
Molecular Note A polIIsneopA cassette was inserted to replace exons 2 and 3, which encode the first 123 of 225 amino acids. Northern blot and immunoblot failed to detect wild type transcript and protein, respectively. An aberrant transcript was detected, possibly due to an initiation site in exons 1a or 1b and splicing directly to exon 4, 5 or 6. In such a transcript, the first available start codon is in exon 5, and, if translated, this transcript would yield a 23 amino-acid peptide. [MGI Ref ID J:101203]

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Genotyping Protocols

Insig1tm1Mbjg
Insig2tm1Mbjg

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as homozygotes at both loci.
Diet Information LabDiet® 5K52/5K67

Animal Health Reports

Room Number           AX11

Research Applications

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

Cardiovascular Research
Hypercholesterolemia
Hypocholesterolemia

Diabetes and Obesity Research
Hyperinsulinemia
Hypoinsulinemia
Insulin Receptors and Growth Factors
Insulin Resistance

Internal/Organ Research
Liver Defects

Metabolism Research
Lipid Metabolism

Research Tools
Endocrine Deficiency Research
Metabolism Research

References

Selected Reference(s)

Engelking LJ; Liang G; Hammer RE; Takaishi K; Kuriyama H; Evers BM; Li WP; Horton JD; Goldstein JL; Brown MS. 2005. Schoenheimer effect explained - feedback regulation of cholesterol synthesis in mice mediated by Insig proteins. J Clin Invest 115(9):2489-98. [PubMed: 16100574]  [MGI Ref ID J:101203]

Additional References

Price and Supply Information

Strain Name: B6;129S6-Insig1tm1Mbjg Insig2tm1Mbjg/J
Stock Number: 005939

Price Details

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
- Use of MICE by companies or for-profit entities requires a license.

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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