C57BL/6J-Tg(Prnp-CHCHD10*S59L)U1Dkan/J

Stock number: 037783
Product name: CHCHD10-S59L
Research areas: Cell Biology Research, Metabolism Research, Neurobiology Research

Description

CHCHD10-S59L mice harbor the human S59L mutation in the coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) transgene driven by the endogenous prion (Prnp) promoter. These mice may be useful for studying amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and mitochondrial myopathies.

The donating laboratory has made multiple Prnp-CHCHD10 transgenic lines available: CHCHD10-WT (Stock No. 037781), CHCHD10-R15L (Stock No. 037782) and CHCHD10-S59L (Stock No. 037783).

Detailed description

Coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) is a mitochondrial protein that is involved with maintaining cristae morphology and regulating oxidative phosphorylation. Chchd10 mutations have been associated with neurodegenerative and neuromuscular diseases such as spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and other mitochondrial myopathies.

CHCHD10-S59L mice harbor the human S59L mutant CHCHD10 cDNA driven by the mouse prion promoter (Prnp), resulting in transgene expression exclusively in neuronal cells. Hemizygous CHCHD10-S59L mice are viable and fertile; it is unknown if homozygous CHCHD10-S59L mice are viable. These mice demonstrate increased expression of CHCHD10 protein in the brain and spinal cord (~2.5 fold increase to endogenous levels). CHCHD10-S59L hemizygous mice exhibit impaired mitochondrial function, significantly increased CHCHD10 aggregation and phospho-TDP-43 pathology as well as poor motor coordination, muscle strength and sciatic nerve function by 10 months of age. The neurological phenotype in the CHCHD10-S59L mice appears to be more severe than that of the CHCHD10-R15L hemizygous mice (Stock No. 037782).

The donating laboratory has made multiple Prnp-CHCHD10 transgenic lines available: CHCHD10-WT (Stock No. 037781), CHCHD10-R15L (Stock No. 037782) and CHCHD10-S59L (Stock No. 037783).

Development

The CHCHD10-S59L transgene was generated using FLAG-tagged CHCHD10 S59L mutant cDNA cloned into the expression vector MoPrP.Xho, which contains the mouse genomic prion promoter (Prnp) sequence. Purified linearized DNA was microinjected into the pronuclei of fertilized C57BL/6J oocytes. Founder line U1 was established and maintained by crossing hemizygous CHCHD10-S59L mice to C57BL/6 mice. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (Stock No. 000664) oocytes.

As per the donating investigator, the insertion site and transgene copy number have not been confirmed. The donating laboratory has also indicated that mice with agouti coat color are occasionally seen in the colony.

Allele

Symbol: Tg(Prnp-CHCHD10*S59L)U1Dkan
Name: transgene insertion U1, David Kang
MGI accession ID: MGI:7380626
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence; Epitope tag
Synonyms: CHCHD10-S59L
Marker symbol: Tg(Prnp-CHCHD10*S59L)U1Dkan
Marker name: transgenic insertion U1, David Kang
Chromosome: UN
Strain of origin: C57BL/6J
Molecular note: The transgenic construct contains a FLAG-tagged CHCHD10 S59L mutant cDNA cloned into the expression vector MoPrP.Xho, which contains the mouse genomic prion promoter (Prnp) sequence.