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
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Sirt4 | sirtuin 4 |
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 |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Sirt4tm1Lgu |
Gene Symbol and Name | Sirt4, sirtuin 4 |
Gene Synonym(s) | |
Site of Expression | lacZ is expressed in the mitochondria of β cells. |
Strain of Origin | 129S1/Sv-Oca2+ Tyr+ Kitl+ |
Chromosome | 5 |
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Sirt4<tm1Fwa> |
Frozen Mouse Embryo | 129-Sirt4<tm1Fwa>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | 129-Sirt4<tm1Fwa>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | 129-Sirt4<tm1Fwa>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | 129-Sirt4<tm1Fwa>/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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