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

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

Nature communications (2020-10-22)
Ching Serena Kao, Rebekah van Bruggen, Jihye Rachel Kim, Xiao Xiao Lily Chen, Cadia Chan, Jooyun Lee, Woo In Cho, Melody Zhao, Claudia Arndt, Katarina Maksimovic, Mashiat Khan, Qiumin Tan, Michael D Wilson, Jeehye Park
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-MATR3 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-GAPDH Mouse mAb (6C5), liquid, clone 6C5, Calbiochem®
Sigma-Aldrich
Harris Hematoxylin Solution, Modified
Sigma-Aldrich
DL-Glyceraldehyde 3-phosphate solution, 45-55 mg/mL in H2O