129-Sirt7^tm1Fwa/J

Stock number: 012771
Product name: SIRT7 KO

Description

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.

Detailed description

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.

Development

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.

Allele

Symbol: Sirt7^tm1Fwa
Name: targeted mutation 1, Frederick W Alt
MGI accession ID: MGI:4441347
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Sirt7
Marker name: sirtuin 7
Chromosome: 11
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Expressed genes: lacZ,beta-galactosidase,E. coli
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.