bioRxiv preprint doi: https://doi.org/10.1101/2020.05.22.110098; this version posted May 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Targeting the RHOA pathway improves learning and memory in Kctd13 and 16p11.2 deletion mouse models. Authors Sandra MARTIN LORENZO1, Valérie NALESSO1, Claire CHEVALIER1, Marie-Christine BIRLING2, and Yann HERAULT1,2,*. Affiliations 1 Université de Strasbourg, CNRS, INSERM, Institut de Génétique Biologie Moléculaire et Cellulaire, IGBMC - UMR 7104 - Inserm U1258, 1 rue Laurent Fries, 67404 ILLKIRCH cedex 2 Université de Strasbourg, CNRS, INSERM, CELPHEDIA-PHENOMIN-ICS, Institut Clinique de la Souris, 1 rue Laurent Fries, 67404 ILLKIRCH cedex *Corresponding author: Yann HERAULT,
[email protected] Keywords: Copy number variation, neurodevelopment, intellectual disability, autism spectrum disorders, KCTD13, mouse model, recognition memory. Running title: Therapeutic effects of fasudil in 16p11.2 models. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.05.22.110098; this version posted May 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. HIGHLIGHTS - Kctd13 haploinsufficiency recapitulates most of the behaviour phenotypes found in the 16p11.2 Del/+ models - Fasudil treatment restores Kctd13 and 16p11.2 Del/+ mutant phenotypes in novel location and novel object recognition memory tests - Fasudil treatment restores the RhoA pathway in Kctd13+/- and 16p11.2 Del/+ models ABSTRACT Gene copy number variants (CNV) have an important role in the appearance of neurodevelopmental disorders.