129-Sirt4^tm1Fwa/J

Stock number: 012756
Product name: Sirt4 knockout
Research areas: Diabetes and Obesity Research, Metabolism Research, Research Tools

Description

These Sirt4 knock-out mice may be useful in studying life span and the effects of sirtuin and calorie restriction on amino acid-stimulated insulin secretion and mitochondrial regulation.

Detailed description

The targeted mutation replace exon 1-3 of the mouse sirtuin (silent information regulator 2 (Sir2)) homolog 4 ,Sirt4, gene with a β-galactosidase (lacZ) cassette, abolishing gene function. In these mice lacZ expression is driven by the Sirt4 endogenous promoter and is detected in the mitochondria of β cells. Homozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Sirt4^-/- mice have elevated glutamate dehydrogenase (GDH) activity leading to upregulated glutamine- and leucine-stimulated insulin secretion, but not glucose-stimulated insulin secretion, similar to the effects of calorie restriction (CR= 62 kcal/week). These mice may be useful in studying life span and the effects of sirtuin and calorie restriction on amino acid-stimulated insulin secretion and mitochondrial regulation.

Development

A targeting vector was designed to replace exon 1-3 of the mouse sirtuin (silent information regulator 2 (Sir2)) homolog 4, Sirt4, gene with a β-galactosidase (lacZ) cassette. This construct was electroporated into 129S1/Sv-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric males were bred to 129Sv females and the resulting heterozygous offspring were intercrossed to produce a colony of homozygous Sirt4^-/- 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: Sirt4^tm1Fwa
Name: targeted mutation 1, Frederick W Alt
MGI accession ID: MGI:3769237
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Sirt4
Marker name: sirtuin 4
Chromosome: 5
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Site of expression: lacZ is expressed in the mitochondria of β cells.
Molecular note: Exons 1 through 3 were replaced with a lacZ gene inserted in-frame after the first 21 bp of exon 1. The absence of protein product was confirmed by western blot analysis on brain, pancreas and liver extracts.