The Ser19Stop single nucleotide polymorphism (SNP) of human PHYHIPL affects the cerebellum in mice

Molecular Brain

Hajime Hirase¹  Teiichi Furuichi²  Yoshitake Sano²  Jun-Na Hirota²  Yo Shinoda³  Yasuki Ishizaki⁴  Ayumu Konno⁵  Hirokazu Hirai⁵  Tetsushi Sadakata⁶  Hisako Sugimoto⁶  Izuho Hatada⁷  Takuro Horii⁷ 

[1]Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark

[2]Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, 278-8510, Noda, Chiba, Japan

[3]Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan

[4]Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, 371-8511, Maebashi, Gunma, Japan

[5]Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, 371-8511, Maebashi, Gunma, Japan

[6]Education and Research Support Center, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, 371-8511, Maebashi, Gunma, Japan

[7]Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, 371-8512, Maebashi, Japan

关键词: PHYHIPL;    PHYHIP;    dbSNP;    HapMap Project;    Cerebellum;    Purkinje cell;   

DOI  :  10.1186/s13041-021-00766-x

来源: Springer

【 摘 要 】

The HapMap Project is a major international research effort to construct a resource to facilitate the discovery of relationships between human genetic variations and health and disease. The Ser19Stop single nucleotide polymorphism (SNP) of human phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL) gene was detected in HapMap project and registered in the dbSNP. PHYHIPL gene expression is altered in global ischemia and glioblastoma multiforme. However, the function of PHYHIPL is unknown. We generated PHYHIPL Ser19Stop knock-in mice and found that PHYHIPL impacts the morphology of cerebellar Purkinje cells (PCs), the innervation of climbing fibers to PCs, the inhibitory inputs to PCs from molecular layer interneurons, and motor learning ability. Thus, the Ser19Stop SNP of the PHYHIPL gene may be associated with cerebellum-related diseases.

【 授权许可】

CC BY