Non-canonical role of DNA mismatch repair on sensory processing in mice

Rahman, Sadia N, Neophytou, Demetrios, Oviedo-Gray, Siboney, Vuong, Bao Q, Oviedo, Hysell V (February 2026) Non-canonical role of DNA mismatch repair on sensory processing in mice. Neuroscience, 595. pp. 59-72. ISSN 0306-4522

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Abstract

DNA repair mechanisms are essential for cellular development and function. In post-mitotic neurons, deficiencies in DNA damage response proteins can lead to severe neurodegenerative and neurodevelopmental disorders. One highly conserved factor involved in DNA repair is MutS Homolog 2 (Msh2), which is responsible for correcting base-base mismatches and insertion/deletion loops during cell proliferation. However, its role in mature neurons remains poorly understood. This study investigates the impact of Msh2 loss on sensory processing in mice. Using electrophysiological and molecular assays, we identifiedsignificant deficits in cortical and thalamic sound processing in Msh2-/- mice. These deficits were linked to dysfunction of the thalamic reticular nucleus (TRN), which critically regulates corticothalamic and thalamocortical activity. Our findings revealed increased oxidative damage, aberrant neuronal activity, and elevated parvalbumin (PV) expression in PV+ neurons in the TRN of Msh2-/- mice. Additionally, we observed the presence of connexin plaques, indicating that disrupted gap junction formation may contribute to impaired TRN function. These results highlight Msh2's crucial role in supporting PV+ neurons in the TRN, profoundly influencing sensory processing. This study provides new insight into how DNA repair mechanisms regulate neuronal development and function in a region-specific manner, potentially contributing to our understanding of their role in neurological disorders.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organism description > animal bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA repair organism description > animal > mammal organism description > animal > mammal > rodent > mouse organism description > animal > mammal > rodent
CSHL Authors:	Rahman, Sadia
Communities:	CSHL labs > Shea lab School of Biological Sciences > Publications
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	16 February 2026
Date Deposited:	17 Feb 2026 13:44
Last Modified:	17 Feb 2026 13:44
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/42088

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