Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology

Éanna B. Ryan, Jianhua Yan, Nimrod Miller, Sudarshan Dayanidhi, Yongchao C. Ma, Han Xiang Deng, Teepu Siddique*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) have been identified in patients suffering from various degenerative diseases including mitochondrial myopathy, spinal muscular atrophy Jokela type, frontotemporal dementia, and/or amyotrophic lateral sclerosis (ALS). The pathogenic mechanism underlying CHCHD10-linked divergent disorders remains largely unknown. Here we show that transgenic mice overexpressing an ALS-linked CHCHD10 p.R15L mutation leads to an abbreviated lifespan compared with CHCHD10-WT transgenic mice. The occurrence and severity of the phenotype correlates to transgene copy number. Central nervous system (CNS), skeletal muscle, and cardiac pathology is apparent in CHCHD10-R15L transgenic mice. Despite the pathology, CHCHD10-R15L transgenic mice perform comparably to control mice in motor behavioral tasks until very close to death. Although paralysis is not observed, these models provide insight into the pleiotropic nature of CHCHD10 and suggest a contribution of CNS, skeletal muscle, and cardiac pathology to CHCHD10 p.R15L-ALS pathogenesis.

Original languageEnglish (US)
Article number102061
JournaliScience
Volume24
Issue number2
DOIs
StatePublished - Feb 19 2021

Keywords

  • Molecular Biology
  • Molecular Physiology
  • Neuroscience

ASJC Scopus subject areas

  • General

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