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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
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+F4pN1
Generation DefinitionsDonating Investigator Dr. Frederick W. 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 (256 strains)
017334 STOCK Sirt6tm1.1Cxd/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Sirt6tm1Fwa/Sirt6tm1Fwa
involves: 129X1/SvJ
- mortality/aging
- complete lethality at weaning
- fail to thrive and die around P24 (MGI Ref ID J:112817)
- cellular phenotype
- abnormal lymphopoiesis
- 10-fold reduction in the number of splenic lymphoctes (MGI Ref ID J:112817)
- decreased cell proliferation
- in MEFs and ES cells (MGI Ref ID J:112817)
- increased cellular sensitivity to alkylating agents
- 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 (MGI Ref ID J:112817)
- increased cellular sensitivity to ionizing radiation
- 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 (MGI Ref ID J:112817)
- 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 (MGI Ref ID J:112817)
- spontaneous chromosome breakage
- increase in the frequency of fragmented chromosome, detached centromeres and chromosomal gaps in metaphase spreads from early and late passage MEFs (MGI Ref ID J:112817)
- spectral karyotype analysis detects increases in the frequency of chromosome breaks, translocations, and dicentric chromosomes (MGI Ref ID J:112817)
- growth/size phenotype
- decreased body size
- significantly smaller by about 10 days of age (MGI Ref ID J:112817)
- postnatal growth retardation
- similar size at birth but significantly smaller by about 10 days of age; however food intake is normal (MGI Ref ID J:112817)
- adipose tissue phenotype
- decreased subcutaneous adipose tissue amount
- acute loss beginning around 3 weeks of age (MGI Ref ID J:112817)
- digestive/alimentary phenotype
- colitis
- consisting of erosion of the superficial colonic epithelium beginning around 3 weeks of age (MGI Ref ID J:112817)
- hematopoietic system phenotype
- abnormal lymphopoiesis
- 10-fold reduction in the number of splenic lymphoctes (MGI Ref ID J:112817)
- decreased bone marrow cell number
- 10-fold reduction in the number of B cell progenitors in the bone marrow (MGI Ref ID J:112817)
- decreased leukocyte cell number
- decreased double-positive T cell number
- 50-fold reduction in the thymus (MGI Ref ID J:112817)
- spleen hypoplasia
- 10-fold reduction in the number of splenic lymphocytes (MGI Ref ID J:112817)
- homeostasis/metabolism phenotype
- decreased circulating glucose level
- decreases rapidly in mice older than 12 days of age, dropping below detection limits by 24 days of age (MGI Ref ID J:112817)
- decreased circulating insulin-like growth factor I level
- serum levels of insulin like growth factor (IGF1) are low at 12 days of age and severely by 19 days of age (MGI Ref ID J:112817)
- skeleton phenotype
- decreased bone mineral density
- 30% reduction in bone mineral density at about 3 weeks of age (MGI Ref ID J:112817)
- kyphosis
- lordokyphosis visible around 3 weeks of age (MGI Ref ID J:112817)
- lordosis
- lordokyphosis visible around 3 weeks of age (MGI Ref ID J:112817)
- immune system phenotype
- abnormal lymphopoiesis
- 10-fold reduction in the number of splenic lymphoctes (MGI Ref ID J:112817)
- colitis
- consisting of erosion of the superficial colonic epithelium beginning around 3 weeks of age (MGI Ref ID J:112817)
- decreased leukocyte cell number
- decreased double-positive T cell number
- 50-fold reduction in the thymus (MGI Ref ID J:112817)
- spleen hypoplasia
- 10-fold reduction in the number of splenic lymphocytes (MGI Ref ID J:112817)
- integument phenotype
- decreased subcutaneous adipose tissue amount
- acute loss beginning around 3 weeks of age (MGI Ref ID J:112817)
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, Inflammation and Autoimmunity 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 provided by MGI
| Allele Symbol | Sirt6tm1Fwa | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Frederick W Alt | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | SIRT6KO; | ||
| Site of Expression | Expression of lacZ can be detected in most adult and embryonic tissues. | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| General Note | Phenotypic Similarity to Human Syndrome: Progeria (J:112817) | ||
| 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] | ||
| 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; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Sirt6tm1Fwa, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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]
Additional References
Sirt6tm1Fwa relatedBauer I; Grozio A; Lasiglie D; Basile G; Sturla L; Magnone M; Sociali G; Soncini D; Caffa I; Poggi A; Zoppoli G; Cea M; Feldmann G; Mostoslavsky R; Ballestrero A; Patrone F; Bruzzone S; Nencioni A. 2012. The NAD+-dependent histone deacetylase SIRT6 promotes cytokine production and migration in pancreatic cancer cells by regulating Ca2+ responses. J Biol Chem 287(49):40924-37. [PubMed: 23086953] [MGI Ref ID J:192629]
Kawahara TL; Michishita E; Adler AS; Damian M; Berber E; Lin M; McCord RA; Ongaigui KC; Boxer LD; Chang HY; Chua KF. 2009. SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell 136(1):62-74. [PubMed: 19135889] [MGI Ref ID J:147591]
Zhong L; D'Urso A; Toiber D; Sebastian C; Henry RE; Vadysirisack DD; Guimaraes A; Marinelli B; Wikstrom JD; Nir T; Clish CB; Vaitheesvaran B; Iliopoulos O; Kurland I; Dor Y; Weissleder R; Shirihai OS; Ellisen LW; Espinosa JM; Mostoslavsky R. 2010. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 140(2):280-93. [PubMed: 20141841] [MGI Ref ID J:167957]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.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
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2085.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2710.50 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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.
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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 Information
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For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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