Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS
Justin You,
Katarina Maksimovic,
Mark N. Metri,
Anneka Schoeppe,
Karin Chen,
Jooyun Lee,
Jhune Rizsan Santos,
Mohieldin M.M. Youssef,
Michael W. Salter,
Jeehye Park
Affiliations
Justin You
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada
Katarina Maksimovic
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada
Mark N. Metri
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A1, Canada
Anneka Schoeppe
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A1, Canada
Karin Chen
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A1, Canada
Jooyun Lee
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A1, Canada
Jhune Rizsan Santos
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A1, Canada
Mohieldin M.M. Youssef
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada
Michael W. Salter
Neuroscience & Mental Health Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada; Department of Physiology, University of Toronto, ON, M5S 1A8, Canada
Jeehye Park
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A1, Canada; Corresponding author. Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
Microglia have been increasingly implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Dectin-1, encoded by the Clec7a gene, is highly upregulated in a specific microglial response state called disease-associated microglia (DAM) in various neurodegenerative conditions. However, the role of Dectin-1 in ALS is undetermined. Here, we show that Clec7a mRNA upregulation occurs in central nervous system (CNS) regions that exhibit neurodegeneration in a MATR3 S85C knock-in mouse model (Matr3S85C/S85C) of ALS. Furthermore, a significant increase in the number of Dectin-1+ microglia coincides with the onset of motor deficits, and this number increases with disease progression. We demonstrate that the knockout of Dectin-1 does not affect survival, motor function, neurodegeneration, or microglial responses in Matr3S85C/S85C mice. These findings suggest that Dectin-1 does not play a role in modifying ALS onset or progression.
