Killam Seminar Series: Identifying the Early Events in ALS Pathogenesis in MATR3 S85C KI Mice

Grâce à la générosité des fiducies Killam, Le Neuro convoque lors d’une série de séminaires des conférenciers d’exception dont les travaux passionnent ses chercheurs et ceux de l’Université McGill. 

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Jeehye Park, PhD

Scientifique principale, Institut de recherche SickKids, Professeure associée, Département de génétique moléculaire, Université de Toronto, Canada

Hôte: gary.armstrong [at] mcgill.ca (Gary Armstrong)

Abstract: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that leads to progressive decline in motor impairment, muscle atrophy and paralysis. ALS studies provided significant insights into the disease process, which may involve various molecular pathways and cellular dysfunction that contribute to neurodegeneration. However, we still lack knowledge of how ALS starts to occur and develop, particularly the mechanism underlying the early phase of the disease process. Understanding the early disease stage rather than the late disease stage would enhance our chance of developing effective treatments that could stop or reverse the disease course. To identify the disease-initiating events leading to degeneration, we use our established ALS mouse model, MATR3 S85C knock-in (KI) mice. A missense mutation S85C is the most frequently identified ALS-linked mutation in MATR3, which encodes an RNA binding protein involved in RNA splicing. This newly established ALS model closely mimics the human disease genotype and phenotype, offering enhanced disease relevance compared to existing models in the ALS field and providing an unprecedented opportunity to study the early-stage development and progression of ALS. Using this mouse model, we pursue to 1) determine the early disease events in the disease process and 2) determine how the ALS-linked mutation alters MATR3 function and properties to cause neurodegeneration. Our findings will uncover the early disease process, which may change the view of how ALS develop and progress. Defining the key early events will facilitate the development of early prevention and intervention strategies for ALS.