Bibliographic Details
| Title: |
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 |
| 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 |
| Source: |
Advanced Science, Vol 12, Iss 14, Pp n/a-n/a (2025) |
| Publisher Information: |
Wiley, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Science |
| Subject Terms: |
5p15.2 deletion, Cri du Chat syndrome, Ctnnd2, gene therapy, rat model, Science |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2198-3844 |
| Relation: |
https://doaj.org/toc/2198-3844 |
| DOI: |
10.1002/advs.202415224 |
| Access URL: |
https://doaj.org/article/43136cab7be8424eb849d4363c8f6c58 |
| Accession Number: |
edsdoj.43136cab7be8424eb849d4363c8f6c58 |
| Database: |
Directory of Open Access Journals |
