Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS

Abstract

AbstractMicroglia have been increasingly implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Dectin-1, encoded by theClec7agene, 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 thatClec7amRNA 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 severity. We demonstrate that the knockout of Dectin-1 does not affect survival, motor function, neurodegeneration, or microglial responses inMatr3S85C/S85Cmice. These findings suggest that Dectin-1 does not play a role in modifying ALS onset or progression but could potentially serve as a valuable biomarker for ALS severity.Subject areasPhysiology; Molecular biology; Neuroscience; ImmunologyHighlightsClec7aupregulation is confined to central nervous system regions that exhibit overt neurodegeneration in a MATR3 S85C knock-in mouse model of ALSThe appearance of Dectin-1+microglia coincides with the onset of motor deficits, and its number increases with disease progressionKnockout of Dectin-1 does not modify survival, motor deficits, neurodegeneration, or microglial responses in MATR3 S85C knock-in mice