Sirt2tm1.1Fwa mice exhibit genomic instability and chromosomal aberrations, and are prone to tumorigenesis. These mice may be useful in studies of necroptosis and tumorigenesis.
Dr. Frederick W. Alt, Children's Hospital
Loss of SIRT2 is associated with greater genome instability in that SIRT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of histone H4 (H4K16Ac), an epigenetic
mark that has been proposed to directly regulate chromatin. Sirt2tm1.1Fwa mice are also prone to tumorigenesis.
Mice from this strain have been used to study the role of sirtuin 2 (silent mating type information regulation 2, homolog) 2 in programmed necrosis (necroptosis), which may have important implications in the cellular response to a host of insults, including bacterial and viral infection, various neurodegenerative processes, as well as ischaemia-reperfusion injury of the brain and heart.
A targeting vector was designed to replace exon 5-6 and part of exon 7 of the mouse sirtuin (silent information regulator 2 (Sir2)) homolog 2, Sirt2 gene with a floxed neomycin (neo)-resistance cassette. This construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre expression plasmid for the purpose of removing the neo cassette. ES cells that had successfully undergone Cre-mediated recombination and no longer retained the cassette were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to 129/Sv females. These mice were then backcrossed to C57BL/6 for 8 generations to produce homozygous Sirt2-/- mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1.1, Frederick W Alt|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Sirt2, sirtuin 2|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A targeting vector was designed to replace exon 5-6 and part of exon 7 with a floxed PGK-neomycin (neo)-resistance cassette. Cre-mediated recombination removed the neo cassette.|
|Mutations Made By|| |
Dr. Frederick Alt, Children's Hospital
When maintaining a live colony, homozygous mice may be bred.
When using the Sirt2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #012772 in your Materials and Methods section.