STOCK Sirt6^tm1.1Cxd/J

Stock number: 017334
Product name: Sirt6^c , Sirt6^Co , Sirt6^flox
Research areas: Metabolism Research, Neurobiology Research, Research Tools

Description

These Sirt6^Co floxed mutant mice possess loxP sites flanking exons 2-3 of the sirtuin 6 (Sirt6) targeted gene. This strain may be useful for studying glycoloysis, lipid metabolism, and glucose homeostasis.

Detailed description

These Sirt6^Co floxed mutant mice possess loxP sites flanking exons 2-3 of the sirtuin 6 (Sirt6) targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Sirt6 is a histone deacetylase highly expressed in the central nervous system, which is involved in the regulation of glucose homeostasis, cell fate, and genomic stability. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 2-3 deleted in cre-expressing tissues.

For example, when crossed to a strain expressing Nestin-Cre in the central and peripheral nervous system (see Stock No. 003771), this mutant mouse strain exhibits reduced post-natal growth and obesity.

When crossed to a strain expressing Cre Recombinase in the liver (see Stock No. 016832 or Stock No. 016833), this mutant mouse strain exhibits increased glycolysis, triglyceride synthesis, reduced β oxidation, and fatty liver formation.

Development

A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette upstream of exon 2, and a single loxP site downstream of exon 3 of the sirtuin 6 (Sirt6) gene. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred with Black Swiss females. The resulting offspring were bred to mice expressing Tg(EIIa-cre)C5379Lmgd on an FVB/N background to delete the neo cassette. Resulting offspring contained multiple gene rearrangments; intact floxed-exons 2-3, intact floxed-neo cassette, or excision of exons 2-3 and the neo cassette. The donating investigator reported that mice containing only the floxed-exons were backcrossed to FVB/N mice for at least 20 generations (see SNP note below) to establish a colony of conditional Sirt6 (Sirt6^Co) mice. Upon arrival, mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 9 of the 27 markers throughout the genome were segregating between FVB/NJ and 129, suggesting an incomplete backcross.

Allele

Symbol: Sirt6^tm1.1Cxd
Name: targeted mutation 1.1, Chu-Xia Deng
MGI accession ID: MGI:4847905
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Sirt6
Marker name: sirtuin 6
Chromosome: 10
Strain of origin: 129S6/SvEvTac
Molecular note: A loxP site was inserted upstream of exon 2, and an additional loxP site was inserted downstream of exon 3. Cre mediated recombination removed the selection cassette.