Parkinson's disease-like neuromuscular defects occur in prenyl diphosphate synthase subunit 2 (Pdss2) mutant mice

Mitochondrion. 2012 Mar;12(2):248-57. doi: 10.1016/j.mito.2011.09.011. Epub 2011 Oct 1.


The Pdss2 gene product is needed for the isoprenylation of benzoquinone to generate coenzyme Q (CoQ). A fatal kidney disease occurs in mice that are homozygous for a missense mutation in Pdss2, which can be recapitulated in conditional Pdss2 knockouts targeted to glomerular podocytes. We now report that homozygous missense mutants also demonstrate significant neuromuscular deficits, as validated by behavioral and coordination assays, and these deficits are recapitulated in conditional Pdss2 knockouts targeted to dopaminergic neurons. Both conditional knockout and missense mutant mice demonstrate deficiencies in tyrosine hydroxylase-positive neurons in the substantia nigra, implicating a pathology similar to sporadic Parkinson's disease (PD).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / genetics*
  • Alkyl and Aryl Transferases / metabolism*
  • Animals
  • Gene Knockout Techniques
  • Homozygote
  • Male
  • Mice
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / pathology*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism*
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Mutation, Missense
  • Neuromuscular Diseases / genetics
  • Neuromuscular Diseases / pathology*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism


  • Mitochondrial Proteins
  • Mutant Proteins
  • Protein Subunits
  • Alkyl and Aryl Transferases
  • prenyl diphosphate synthase subunit 2, mouse