动物造模,自噬基因 z-bio 2021-10-18 624

　　Through the method of genetic selection 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 base of epg-6 gene in mammals is due to WDR45/WIPI4. WDR45 encodes a PtdIn(3)P isolated protein containing a repeat sequence of WD40.

　　Research in human genetics has found that mutations in the WDR45 gene can cause a neurodegenerative disease-BPAN (beta-helix protein-related neurodegenerative disease), which is caused by NBIA (neurodegenerative disease associated with 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 show reduced motor harmony and severely impaired learning and memory functions. Histopathological and immunohistochemical studies found that the brain of Wdr45 knockout mice showed severe axon edema, accompanied by the accumulation of a large number of eosinophils, and the autophagy pathway was inhibited in neurons and edematous axons. The autophagy substrates SQSTM1 and ubiquitin accumulate significantly.

　　"To sum up, the Wdr45 gene mice (Nes-Wdr45fl/Y mice) showed locally similar phenotypes to BPAN patients, including cognitive impairment and imbalance of axon homeostasis. Therefore, this study helps to further understand the pathogenesis of BPAN, and also helps to deepen the study of the role of autophagy in maintaining axon homeostasis.