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

Mol Brain. 2021 Mar 12;14(1):52. doi: 10.1186/s13041-021-00766-x.

Abstract

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.

Keywords: Cerebellum; HapMap Project; PHYHIP; PHYHIPL; Purkinje cell; dbSNP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CRISPR-Cas Systems
  • Cell Shape
  • Cerebellum / cytology*
  • Codon, Terminator
  • Female
  • Gene Knock-In Techniques
  • HapMap Project
  • Humans
  • Interneurons / physiology
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Activity
  • Nerve Fibers / physiology
  • Polymorphism, Single Nucleotide*
  • Purkinje Cells / metabolism
  • Purkinje Cells / ultrastructure*
  • Rotarod Performance Test
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • Codon, Terminator
  • Intracellular Signaling Peptides and Proteins
  • PHYHIPL protein, human