These Risp+/P224S mutant mice exhibit mildly impaired mitochondrial function, reduced metabolic rate (heterozygous males), and may have applications in studies of longevity, aging and mitochondrial function.
Siegfried Hekimi, McGill University
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted | Uqcrfs1 | ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 |
Ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1, is a subunit of the ubiquinol-cytochrome c reductase complex (Complex III or Cytochrome bc1 complex), of the electron transport chain, which transfers electrons from ubiquinol to cytochrome c.
These mice carry a targeted mutation of the Uqcrfs1 gene, consisting of a proline-to-serine point mutation(P224S) in exon 2 that corresponds to the mutation found in isp-1(qm150) mutant Caenorhabditis elegans worms. Mice that are homozygous for the targeted mutation have an embryonic lethal phenotype. Heterozygotes are viable and fertile. Heterozygous males have a lifespan that is 10% less than wildtype controls. Female heterozygotes have an unaffected median lifespan, but those that survive to mid-life exhibit a survival advantage relative to wild type controls. Male heterozygotes, 3 months of age, exhibit decreased metabolic rate, while 3 month old heterozygous females and 2 year old heterozygotes do not. Two-year old heterozygous males exhibit impaired motor learning relative to wild type controls. A lower amount of gene product (protein) is detected by Western blot analysis of mitochondria isolated from liver of heterozygotes; the protein level is estimated to be approximately 67% of the wildtype level. Complex III enzymatic activity is reduced in liver by 20% in male heterozygotes and 15% in female heterozygotes.
A targeting vector containing a FRT site flanked NEO cassette was used to replace the proline 224 codon CCC with TCG in exon 2. The construct was electroporated into unspecified C57BL/6 derived embryonic stem (ES) cells (Ingenko), which were transiently transfected with a FLPe recombinase vector to remove the selection cassette. ES cells that had successfully undergone FLPe-mediated recombination and no longer retained the cassette were injected into blastocysts. The resulting mice were backcrossed to C57BL/6J for 6 generations. Sequencing revealed a 33 bp duplication adjacent to the remaining FRT site.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
Allele Name | targeted mutation 1.1, Siegfried Hekimi |
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Allele Type | Targeted |
Allele Synonym(s) | RispP224S |
Gene Symbol and Name | Uqcrfs1, ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 |
Gene Synonym(s) | |
Promoter | Uqcrfs1, ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1, mouse, laboratory |
Strain of Origin | C57BL/6 |
Chromosome | 13 |
Molecular Note | Nucleotide substitutions (CCC to TCG) result in the amino acid substitution of serine for proline at position 224 (P224S). This mutation is equivalent to one found in long-lived isp-1 (qm150) worms. Flp-mediated recombination removed the neo cassette used for selection purposes. |
When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes have an embryonic lethal phenotype.
When using the C57BL/6-Uqcrfs1tm1.1Hek/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017721 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wildtype for Uqcrfs1<tm1.1Hek> |
Frozen Mouse Embryo | C57BL/6-Uqcrfs1<tm1.1Hek>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Uqcrfs1<tm1.1Hek>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Uqcrfs1<tm1.1Hek>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | C57BL/6-Uqcrfs1<tm1.1Hek>/J Frozen Embryo | $3373.50 |
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