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| This mutant mouse strain contains a lacZ gene knock-in resulting in a loss of function of the targeted allele and may be useful in studies of DNA damage repair, genomic stability, and aging. | |||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation ?+F3 (01-MAY-08) Donating Investigator Frederick Alt, Children's Hospital Description
Homozygous neonates are smaller than their wildtype and heterozygous littermates. They develop normally until approximately 21 days of age, when they develop an acute and rapid, aging-like degenerative pathology resulting in death by postnatal day 24. Homozygous mutant mice exhibit subcutaneous fat loss, lordokyphosis (hunchbacked spine) with osteopenia (30% loss of bone mineral density), colitis, and severe lymphopenia due to increased lymphocyte apoptosis. At day 12, mice have reduced insulin-like growth factor I (IGF-1) levels in serum, and develop severe hypoglycemia. Mouse embryonic fibroblasts (MEFs) prepared from homozygous embryos exhibit reduced proliferation, defective base excision repair function, as indicated by increased sensitivity to alkylating agents and ionizing radiation, and increased chromosomal aberrations. The donating investigators report that no gene product (mRNA or protein) is detected by RT-PCR or immuoblot analysis of tissues, MEFs or embryonic stem cells from homozygotes. The targeting construct placed a lacZ expression cassette in frame into exon 1 of the mRNA coding sequence, and beta-galactosidase staining is detected in most adult and embryonic tissues. This mutant mouse strain may be useful in studies related to DNA damage repair, genomic stability, and aging.Development
A targeting vector containing the lacZ and neomycin resistance genes was used to disrupt exons 1 to 6. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were crossed to 129X1/SvJ female mice.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (176 strains)
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Sirt6tm1Fwa/Sirt6tm1Fwa
involves: 129X1/SvJ
- lethality-postnatal
- lethality at weaning (MGI Ref ID J:112817)
- fail to thrive and die around P24
- cellular phenotype
- decreased cell proliferation (MGI Ref ID J:112817)
- in MEFs and ES cells
- increased cellular sensitivity to alkylating agents (MGI Ref ID J:112817)
- increased sensitivity of MEFs to monofunctional alkylating agents suggesting a defect in base excision repair; however double strand break repair and nucleotide excision repair are similar to wild-type
- increased cellular sensitivity to ionizing radiation (MGI Ref ID J:112817)
- increased DNA damage and reduced survival in MEFs and ES cells following exposure to ionizing radiation; however, UV sensitivity of MEFs is similar to wild-type cells
- thymocytes from 21 day old mice display increased sensitivity to IR and monofunctional alkylating agents; however sensitivity of cells from 12 day old mice is similar to wild-type
- spontaneous chromosome breakage (MGI Ref ID J:112817)
- increase in the frequency of fragmented chromosome, detached centromeres and chromosomal gaps in metaphase spreads from early and late passage MEFs
- spectral karyotype analysis detects increases in the frequency of chromosome breaks, translocations, and dicentric chromosomes
- growth/size phenotype
- decreased body size (MGI Ref ID J:112817)
- significantly smaller by about 10 days of age
- postnatal growth retardation (MGI Ref ID J:112817)
- similar size at birth but significantly smaller by about 10 days of age; however food intake is normal
- adipose tissue phenotype
- decreased subcutaneous adipose tissue amount (MGI Ref ID J:112817)
- acute loss beginning around 3 weeks of age
- digestive/alimentary phenotype
- colitis (MGI Ref ID J:112817)
- consisting of erosion of the superficial colonic epithelium beginning around 3 weeks of age
- hematopoietic system phenotype
- abnormal lymphopoiesis (MGI Ref ID J:112817)
- 10-fold reduction in the number of splenic lymphoctes
- abnormal B cell differentiation (MGI Ref ID J:112817)
- 10-fold reduction in the number of B cell progenitors in the bone marrow
- decreased double-positive T cell number (MGI Ref ID J:112817)
- 50-fold reduction in the thymus
- abnormal spleen cellularity (MGI Ref ID J:112817)
- 10-fold reduction in the number of splenic lymphoctes
- decreased bone marrow cell number (MGI Ref ID J:112817)
- 10-fold reduction in the number of B cell progenitors in the bone marrow
- decreased leukocyte cell number (MGI Ref ID J:112817)
- severe lymphopenia associated with increased lymphocyte apoptosis
- adoptive transfer studies indicate increased lymphocyte apoptosis is not a cell intrinsic defect
- decreased double-positive T cell number (MGI Ref ID J:112817)
- 50-fold reduction in the thymus
- homeostasis/metabolism phenotype
- decreased circulating glucose level (MGI Ref ID J:112817)
- decreases rapidly in mice older than 12 days of age, dropping below detection limits by 24 days of age
- decreased circulating insulin-like growth factor I level (MGI Ref ID J:112817)
- serum levels of insulin like growth factor (IGF1) are low at 12 days of age and severely by 19 days of age
- skeleton phenotype
- decreased bone density (MGI Ref ID J:112817)
- 30% reduction in bone mineral density at about 3 weeks of age
- kyphosis (MGI Ref ID J:112817)
- lordokyphosis visible around 3 weeks of age
- lordosis (MGI Ref ID J:112817)
- lordokyphosis visible around 3 weeks of age
- immune system phenotype
- abnormal lymphopoiesis (MGI Ref ID J:112817)
- 10-fold reduction in the number of splenic lymphoctes
- abnormal B cell differentiation (MGI Ref ID J:112817)
- 10-fold reduction in the number of B cell progenitors in the bone marrow
- decreased double-positive T cell number (MGI Ref ID J:112817)
- 50-fold reduction in the thymus
- abnormal spleen cellularity (MGI Ref ID J:112817)
- 10-fold reduction in the number of splenic lymphoctes
- colitis (MGI Ref ID J:112817)
- consisting of erosion of the superficial colonic epithelium beginning around 3 weeks of age
- decreased leukocyte cell number (MGI Ref ID J:112817)
- severe lymphopenia associated with increased lymphocyte apoptosis
- adoptive transfer studies indicate increased lymphocyte apoptosis is not a cell intrinsic defect
- decreased double-positive T cell number (MGI Ref ID J:112817)
- 50-fold reduction in the thymus
This mouse can be used to support research in many areas including:
Apoptosis Research
Endogenous Regulators
Cancer Research
Other (DNA Repair)
Cardiovascular Research
Other (altered fat metabolism)
Cell Biology Research
DNA Damage Response
Immunology and Inflammation Research
Immunodeficiency (Inflammatory bowel disease)
Inflammation (Inflammatory bowel disease)
Lymphoid Tissue Defects
Internal/Organ Research
Gastrointestinal Defects (colitis)
Lymphoid Tissue Defects
Research Tools
lacZ Expression
Apoptosis Research
Internal/Organ Research
Metabolism Research
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Sirt6tm1Fwa | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Frederick W Alt | ||
| Allele Type | Targeted (knock-out) | ||
| Site of Expression | Expression of lacZ can be detected in most adult and embryonic tissues. | ||
| Gene Symbol and Name | Sirt6, sirtuin 6 (silent mating type information regulation 2, homolog) 6 (S. cerevisiae) | ||
| Chromosome | 10 | ||
| Gene Common Name(s) | 2810449N18Rik; AI043036; RIKEN cDNA 2810449N18 gene; SIR2L6; expressed sequence AI043036; | ||
| General Note | Phenotypic Similarity to Human Syndrome: Progeria | ||
| Molecular Note | A LacZ gene was inserted in frame after the first 21 bp of exon 1 via homologous recombination replacing exons 1 to 6. [MGI Ref ID J:112817] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Sirt6tm1Fwa, SEP PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Mostoslavsky R; Chua KF; Lombard DB; Pang WW; Fischer MR; Gellon L; Liu P; Mostoslavsky G; Franco S; Murphy MM; Mills KD; Patel P; Hsu JT; Hong AL; Ford E; Cheng HL; Kennedy C; Nunez N; Bronson R; Frendewey D; Auerbach W; Valenzuela D; Karow M; Hottiger MO; Hursting S; Barrett JC; Guarente L; Mulligan R; Demple B; Yancopoulos GD; Alt FW. 2006. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124(2):315-29. [PubMed: 16439206] [MGI Ref ID J:112817]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation do not survive past postnatal day 24 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Heterozygous for Sirt6tm1Fwa *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Heterozygous for Sirt6tm1Fwa x Wild-type for Sirt6tm1Fwa $288.65 Wild-type for Sirt6tm1Fwa x Heterozygous for Sirt6tm1Fwa
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Heterozygous for Sirt6tm1Fwa *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Heterozygous for Sirt6tm1Fwa x Wild-type for Sirt6tm1Fwa $375.30 Wild-type for Sirt6tm1Fwa x Heterozygous for Sirt6tm1Fwa
Additional Supply Details
| Supply Notes |
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Supply Details
| Standard Supply | Repository-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. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 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. | ||
General Terms and Conditions
See Terms of Use
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.Ordering and Purchasing Information
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Terms of Use
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General Terms and Conditions
For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.
Contact information
General inquiries
Contracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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