Sex specific disruptions in PKCG signaling in a mouse model of Spinocerebellar Ataxia Type 14
We have developed a new Spinocerebellar Ataxia Type 14 (SCA14) mouse model with amino acid deletion Phe48 (deltaF48) in PKCG identified in human patients. The severe biochemical defects of deltaF48 PKCG are associated with early age of onset and high disease severity. To understand the pathology of deltaF48 PKCG-induced SCA14, a deltaF48 PKCG knock-in mouse was generated with CRISPR/Cas9-mediated genome editing methods. This mouse model of SCA14 was validated through whole genome sequencing and off-target analysis. The deltaF48 PKCG mouse displayed ataxia-associated phenotypes that were more severe in males compared with females.