Mouse model of chorea-acanthocytosis exhibits male infertility caused by impaired sperm motility as a result of ultrastructural morphological abnormalities in the mitochondrial sheath in the sperm midpiece

Biochem Biophys Res Commun. 2018 Sep 5;503(2):915-920. doi: 10.1016/j.bbrc.2018.06.096. Epub 2018 Jun 21.


Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis caused by loss-of-function mutations in the Vacuolar Protein Sorting 13 Homolog A (VPS13A) gene, which encodes chorein. We previously produced a ChAc-model mouse with a homozygous deletion of exons 60-61 in Vps13a, which corresponded to the human disease mutation. We found that male ChAc-model mice exhibited complete infertility as a result of severely diminished sperm motility. Immunocytochemical study revealed that chorein-like immunoreactivity is abundant only in the midpiece, mitochondria-rich region, of the sperm of wild type mice. They showed no significant differences from wild types in terms of the adenosine 5'-triphosphate (ATP) concentration of their sperm, sperm count, or sexual activity. Electron microscopy revealed abnormal ultrastructural morphology of the mitochondria in the midpiece of sperm from ChAc-model mice. These results suggest that chorein is essential in mouse sperm for the maintenance of ultrastructural mitochondrial morphology and sperm motility.

Keywords: Asthenozoospermia; ChAc-model mouse; Chorea-acanthocytosis; Chorein; Male infertility; Mitochondria; Vps13a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Humans
  • Infertility, Male / genetics*
  • Male
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Neuroacanthocytosis / genetics*
  • Sperm Midpiece / metabolism*
  • Sperm Midpiece / ultrastructure
  • Sperm Motility / genetics*
  • Vesicular Transport Proteins


  • Nerve Tissue Proteins
  • Vesicular Transport Proteins
  • Vps13a protein, mouse