Behavioral Abnormalities, Cognitive Impairments, Synaptic Deficits, and Gene Replacement Therapy in a CRISPR Engineered Rat Model of 5p15.2 Deletion Associated With Cri du Chat Syndrome

• DOI: 10.1002/advs.202415224
• Publication Date: 2025-02-18T19:59:21Z
• Authors: Jingjing Shen; Yan Wang; Yang Liu; Junying Lan; Shuang Long; Yingbo Li; Di Chen; Peng Yu; Jing Zhao; Yongjun Wang; Shali Wang; Feng Yang
• Keywords: Pathogenesis

Abstract The Cri du Chat Syndrome (CdCS), a devastating genetic disorder caused by deletion on chromosome 5p, faces challenges in finding effective treatments and accurate animal models. Using CRISPR‐Cas9, novel CdCS rat model with 2q22 is developed, mirroring common alteration patients. This exhibits pronounced deficits social behavior, cognition, anxiety, accompanied neuronal abnormalities immune dysregulation key brain regions such as the hippocampus medial prefrontal cortex (mPFC). immunostaining RNA‐seq analyses provide new insights into pathogenesis, revealing inflammatory processes. Importantly, it demonstrated that early gene replacement therapy AAV‐ Ctnnd2 alleviates cognitive impairments rats, highlighting potential for intervention. However, effectiveness of this confined to developmental stages does not fully restore all symptoms. findings deepen understanding pathogenesis suggest promising therapeutic directions.