Sirt7 knock-out mice develop chronic hepatosteatosis resembling human fatty liver disease and may be useful for studies of liver metabolism, aging, and a wide spectrum of human diseases.
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 (Reporter, Null/Knockout) | Sirt7 | sirtuin 7 |
These Sirt7 knock-out mice develop chronic hepatosteatosis resembling human fatty liver disease. In SIRT7-deficient cells of these mice, failure to engage SIRT7-mediated ER stress management results in constitutive ER stress that induces activation of the canonical UPR (phosphorylation of eIF2α, blockade of polysome assembly and translational initiation, and induction of ER stress response genes), apoptosis, and inflammation and, specifically in the liver, increased lipogenesis and reduced VLDL secretion.
A targeting vector was designed to replace exons 4-11 of the mouse sirtuin 7 (Sirt7) gene by placing a β-galactosidase (lacZ) cassette, followed by a neo cassette in reverse orientation to the gene, in the 5' end of exon 4. This construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to 129Sv females. These heterozygous mice were bred together to create homozygous Sirt7 KO mice. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression |
Allele Name | targeted mutation 1, Frederick W Alt |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | VG321 |
Gene Symbol and Name | Sirt7, sirtuin 7 |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Strain of Origin | 129S1/Sv-Oca2+ Tyr+ Kitl+ |
Chromosome | 11 |
Molecular Note | A targeting vector was designed to replace exons 4-11 by placing a beta-galactosidase (lacZ) cassette in the 5' end of exon 4. |
Mutations Made By | Dr. Frederick Alt, Children's Hospital |
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or 129S1/SvImJ inbred mice (Stock No. 002448). Homozygous mice are born at a rate lower than the expected Mendelian ratio.
When using the SIRT7 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #012771 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wildtype for Sirt7<tm1Fwa> |
Frozen Mouse Embryo | 129-Sirt7<tm1Fwa>/J | $2595.00 |
Frozen Mouse Embryo | 129-Sirt7<tm1Fwa>/J | $2595.00 |
Frozen Mouse Embryo | 129-Sirt7<tm1Fwa>/J | $3373.50 |
Frozen Mouse Embryo | 129-Sirt7<tm1Fwa>/J | $3373.50 |
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