动物实验,CRISPR/Cas9系统 中国实验动物信息网 2021-10-13 537

　　Through the method of genetic screening of nematodes, the early work of Zhang Hong's research group at the Institute of Biophysics of the Chinese Academy of Sciences found that the epg-6 gene is an important autophagy gene unique to multicellular organisms. The homologous gene of epg-6 gene in mammals is WDR45/WIPI4. WDR45 encodes a PtdIn(3)P binding protein containing WD40 repeats. Human genetics studies have found that mutations in the WDR45 gene can cause a neurodegenerative disease-BPAN (beta-helix protein-related neurodegenerative disease), which is NBIA (neurodegenerative disease accompanied by iron accumulation) A subtype.

　　 In order to study the function of WDR45 gene in mammals, Zhang Hong's group constructed a nervous system-specific Wdr45 gene knockout mouse (Nes-Wdr45fl/Y mouse). Wdr45 gene knockout mice will have reduced motor coordination and severely impaired learning and memory functions. Histopathological and immunohistochemical studies have found that severe axon edema in the brain of Wdr45 knockout mice is accompanied by a large accumulation of eosinophils, and the autophagy pathway is inhibited. The phagocytic substrates SQSTM1 and ubiquitin accumulated significantly. "To sum up, the Wdr45 gene mice (Nes-Wdr45fl/Y mice) have some phenotypes similar to those of BPAN patients, including cognitive impairment and imbalance of axon homeostasis. Therefore, this study will help to further understand the pathogenesis of BPAN, and also help to further study the role of autophagy in maintaining axon homeostasis.