B6.129-Sirt1^tm1Mcby/LguJ

Stock number: 026009
Research areas: Cardiovascular Research, Developmental Biology Research

Description

Sirtuin 1 KO mice may be useful for studying the endothelial expression of genes involved in angiogenesis and endothelial homeostasis, and postnatal vascular growth.

Detailed description

A hygro cassette replaces exons 5-6 of the sirtuin 1 (Sirt1) gene, abolishing gene expression. Heterozygous mice are viable and fertile. Homozygotes are perinatal lethal on inbred backgrounds. The donating investigator reports that F1 crosses of B6 heterozygotes and FVB heterozygotes produces homozygotes at Mendelian ratios. Homozygous F1 offspring are infertile. SIRT1 is a protein deacetylase involved with telomere deacetylation, DNA repair, energy homeostasis. As such SIRT1 plays roles in telomere length maintenance, tumor growth, aging, and improved metabolic syndrome caused by high fat diets. Mice have craniofacial defects, increased apoptosis spermatocytes, and they fail to ovulate. They exhibit micropthalmia, and respiratory, cardiovascular, and immune defects. Some mice develop nephrogenic diabetes insipidus (NDI) characterized by production of large amounts of dilute urine due to the inability of the kidney to concentrate the urine.

Development

A targeting vector was designed to replace exons 5-6 of the sirtuin 1 (Sirt1) gene with a hyrgomycin resistance (hygro) cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into CD1 blastocysts and the resulting chimeric males were bred to 129/Sv females. Mice were then backcrossed at least 10 generations to C57BL/6J background. 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

Symbol: Sirt1^tm1Mcby
Name: targeted mutation 1, Michael W McBurney
MGI accession ID: MGI:2448246
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Sirt1
Marker name: sirtuin 1
Chromosome: 10
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: The gene was disrupted by replacement of exons 5 and 6, which encode a large portion of the catalytic domain, with a hygromycin resistance cassette via homologous recombination. Northern blot analysis of RNA from homozygous mutant E12.5 embryos and adult tissues did not detect gene expression.