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.
Dr. Frederick W. Alt, Children's Hospital
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.
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 Name||targeted mutation 1, Frederick W Alt|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Sirt4, sirtuin 4|
|Site of Expression||lacZ is expressed in the mitochondria of β cells.|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|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.|
|Mutations Made By|| |
Dr. Frederick Alt, Children's Hospital
When maintaining a live colony, homozygous mice may be bred together.
When using the Sirt4 knockout mouse strain in a publication, please cite the originating article(s) and include JAX stock #012756 in your Materials and Methods section.