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
Source abstract
Abstract
Abstract The Cri du Chat Syndrome (CdCS), a devastating genetic disorder caused by a deletion on chromosome 5p, faces challenges in finding effective treatments and accurate animal models. Using CRISPR‐Cas9, a novel CdCS rat model with a 2q22 deletion is developed, mirroring a common genetic alteration in CdCS patients. This model exhibits pronounced deficits in social behavior, cognition, and anxiety, accompanied by neuronal abnormalities and immune dysregulation in key brain regions such as the hippocampus and medial prefrontal cortex (mPFC). The immunostaining and RNA‐seq analyses provide new insights into CdCS pathogenesis, revealing inflammatory and immune processes. Importantly, it is demonstrated that early gene replacement therapy with AAV‐ Ctnnd2 alleviates cognitive impairments in CdCS rats, highlighting the potential for early intervention. However, the effectiveness of this therapy is confined to the early developmental stages and does not fully restore all CdCS symptoms. The findings deepen the understanding of CdCS pathogenesis and suggest promising therapeutic directions.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: CRISPR and Genetic Engineering · Chromosomal and Genetic Variations · Advanced biosensing and bioanalysis techniques
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Institute of Neuroscience School of Basic Medicine Chongqing Medical University Chongqing 400016 China
China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing 100070 China
Basic and Translational Medicine Center China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing 100070 China
Advanced Innovation Center for Human Brain Protection Capital Medical University Beijing 100070 China
Laboratory of Cognitive and Behavioral Disorders Beijing Institute of Brain Disorders Capital Medical University Beijing 100069 China
Chinese Institutes for Medical Research Capital Medical University Beijing 100069 China
Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing 100070 China
Clinical Center for Precision Medicine in Stroke Capital Medical University Beijing 100070 China
Center of Excellence for Omics Research (CORe) Beijing Tiantan Hospital Capital Medical University Beijing 100070 China
Funding
Natural Science Foundation of Beijing Municipality
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