Targeting the RHOA pathway improves learning and memory in adult Kctd13 and 16p11.2 deletion mouse models.

ABSTRACT:

Background

Gene copy number variants play an important role in the occurrence of neurodevelopmental disorders. Particularly, the deletion of the 16p11.2 locus is associated with autism spectrum disorder, intellectual disability, and several other features. Earlier studies highlighted the implication of Kctd13 genetic imbalance in 16p11.2 deletion through the regulation of the RHOA pathway.

Methods

Here, we generated a new mouse model with a small deletion of two key exons in Kctd13. Then, we targeted the RHOA pathway to rescue the cognitive phenotypes of the Kctd13 and 16p11.2 deletion mouse models in a pure genetic background. We used a chronic administration of fasudil (HA1077), an inhibitor of the Rho-associated protein kinase, for six weeks in mouse models carrying a het

SUBMITTER: Martin Lorenzo S 

PROVIDER: S-EPMC7805198 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature