Dataset Information

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

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.

SUBMITTER: Kao CS

PROVIDER: S-EPMC7576598 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Kao Ching Serena CS van Bruggen Rebekah R Kim Jihye Rachel JR Chen Xiao Xiao Lily XXL Chan Cadia C Lee Jooyun J Cho Woo In WI Zhao Melody M Arndt Claudia C Maksimovic Katarina K Khan Mashiat M Tan Qiumin Q Wilson Michael D MD Park Jeehye J

Nature communications 20201020 1

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 ce ...[more]

PMID: 33082323

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Dataset Information

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

Publications

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

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