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

You, J.; Maksimovic, K.; Chen, K.; Lee, J.; Schoeppe, A.; Santos, J. R.; Youssef, M. M. M.; SALTER, M. W.; Park, J.

doi:10.1101/2024.04.18.590117

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bioRxiv · 10.1101/2024.04.18.590117

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

You, J.·Maksimovic, K.·Chen, K.·Lee, J.·Schoeppe, A.·Santos, J. R.·Youssef, M. M. M.·SALTER, M. W.·Park, J.

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Abstract

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 severity. We demonstrate that the knockout of Dectin-1 does not affect survival, motor function, neurodegeneration, or microglial responses in Matr3S85C/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; Immunology HighlightsO_LIClec7a upregulation is confined to central nervous system regions that exhibit overt neurodegeneration in a MATR3 S85C knock-in mouse model of ALS C_LIO_LIThe appearance of Dectin-1+ microglia coincides with the onset of motor deficits, and its number increases with disease progression C_LIO_LIKnockout of Dectin-1 does not modify survival, motor deficits, neurodegeneration, or microglial responses in MATR3 S85C knock-in mice C_LI

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You, J., Maksimovic, K., Chen, K., Lee, J., Schoeppe, A., Santos, J. R., Youssef, M. M. M., SALTER, M. W., Park, J.. 2024-04-22. Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS. https://doi.org/10.1101/2024.04.18.590117

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