CRISPR/cas9 endonuclease mediated genome editing of the Chchd10, coiled-coil-helix-coiled-coil-helix domain containing 10, gene was used to introduce the S55L knock in mutation (TCA -&gt; TTA codon change) in exon 2. The mouse S55L mutation is equivalent to the human S59L mutation. The targeted Chchd10 gene encodes a mitochondrial intermembrane protein that is involved with mitochondrial cristae morphology and oxidative phosphorylation. Mutations in the human CHCHD10 gene can cause frontotemporal dementia and amyotrophic lateral sclerosis (ALS). 
Chchd10S55L heterozygous mice have a shortened mean lifespan of approximately 344 days. Onset of body weight loss and progressive kyphosis is approximately 200 days of age in female heterozygotes and 125 days in male heterozygotes. Homozygotes exhibit a more severe body weight loss compared to heterozygotes. Muscle weakness is apparent at approximately 150 days of age with exercise intolerance, with evident muscle mass loss at 330 days of age. At approximately 260 days of age, heterozygotes exhibit motor deficit (forelimb grip strength) which progresses to abnormal gait. Hypertrophic cardiomyopathy is detected in heterozygotes at 330 days of age. Pregnant female heterozygotes exhibit accelerated mortality compared to virgin female heterozygotes. Histological analysis of heart tissue from breeding heterozygous females reveals cytoplasmic vacuoles, increased variation of the size of the nucleus, and fibrotic interstitial collagen accumulation. Cardiomyocyte ultrastructure is altered (increased number of mitochondria with abnormal features). The myofibers from gastrocnemius muscle exhibit splitting, increased number of atropic and angular fibers, increased nuclear density and central nuclei. Disorganized sarcomeres and increased number of abnormal mitochondria are also observed. Neuromuscular junction innervation and morphology is degenerated and abnormal: approximately 50% of neuromuscular junctions in Chchd10S55L muscle show no innervation.

This CRISPR/Cas9 generated CHCHD10S55L mutant on the C57BL/6NJ background of the of Chchd10 gene introduces the S55L knock-in mutation. These mice may be useful in studies related to mitochondrial bioenergetics and pathogenesis of diseases such as mitochondrial myopathy, motor neuron disease, frontotemporal dementia, Parkinson's disease, and amyotrophic lateral sclerosis.

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