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.
Dr. Frederick W. Alt, Children's Hospital
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Sirt6 | sirtuin 6 |
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.
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.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression | Expression of lacZ can be detected in most adult and embryonic tissues. |
Allele Name | targeted mutation 1, Frederick W Alt |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | SIRT6KO |
Gene Symbol and Name | Sirt6, sirtuin 6 |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Site of Expression | Expression of lacZ can be detected in most adult and embryonic tissues. |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 10 |
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. |
When maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation do not survive past postnatal day 24
When using the 129-Sirt6tm1Fwa/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #006050 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wild-type for Sirt6<tm1Fwa> |
Frozen Mouse Embryo | 129-Sirt6<tm1Fwa>/J | $2595.00 |
Frozen Mouse Embryo | 129-Sirt6<tm1Fwa>/J | $2595.00 |
Frozen Mouse Embryo | 129-Sirt6<tm1Fwa>/J | $3373.50 |
Frozen Mouse Embryo | 129-Sirt6<tm1Fwa>/J | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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