Selective neuronal degeneration in MATR3 S85C knock-in mouse model of early-stage ALS

Nat Commun. 2020 Oct 20;11(1):5304. doi: 10.1038/s41467-020-18949-w.


A missense mutation, S85C, in the MATR3 gene is a genetic cause for amyotrophic lateral sclerosis (ALS). It is unclear how the S85C mutation affects MATR3 function and contributes to disease. Here, we develop a mouse model that harbors the S85C mutation in the endogenous Matr3 locus using the CRISPR/Cas9 system. MATR3 S85C knock-in mice recapitulate behavioral and neuropathological features of early-stage ALS including motor impairment, muscle atrophy, neuromuscular junction defects, Purkinje cell degeneration and neuroinflammation in the cerebellum and spinal cord. Our neuropathology data reveals a loss of MATR3 S85C protein in the cell bodies of Purkinje cells and motor neurons, suggesting that a decrease in functional MATR3 levels or loss of MATR3 function contributes to neuronal defects. Our findings demonstrate that the MATR3 S85C mouse model mimics aspects of early-stage ALS and would be a promising tool for future basic and preclinical research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Disease Models, Animal
  • Female
  • Gene Knock-In Techniques
  • Humans
  • Loss of Function Mutation
  • Male
  • Mice
  • Motor Neurons / metabolism*
  • Mutation, Missense
  • Nuclear Matrix-Associated Proteins / genetics*
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Purkinje Cells / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*


  • Nuclear Matrix-Associated Proteins
  • RNA-Binding Proteins
  • matrin-3 protein, mouse

Associated data

  • figshare/10.6084/m9.figshare.12824312