title: Parkinson's disease-like neuromuscular defects occur in prenyl diphosphate synthase subunit 2 (Pdss2) mutant mice.
abstract: 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).
authors: Department of Genetics, The University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA.
authors: Carly G K
authors: CG
authors: Ziegler
authors: Min
authors: M
authors: Peng
authors: Marni J
authors: MJ
authors: Falk
authors: Erzsebet
authors: E
authors: Polyak
authors: Elpida
authors: E
authors: Tsika
authors: Harry
authors: H
authors: Ischiropoulos
authors: Dana
authors: D
authors: Bakalar
authors: Julie A
authors: JA
authors: Blendy
authors: David L
authors: DL
authors: Gasser
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D055786:Gene Knockout Techniques; D006720:Homozygote; D008297:Male; D051379:Mice; D028361:Mitochondrial Diseases / Q000235:genetics / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D009468:Neuromuscular Diseases / Q000235:genetics / Q000473:pathology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D050505:Mutant Proteins; D021122:Protein Subunits; D019883:Alkyl and Aryl Transferases; C573473:prenyl diphosphate synthase subunit 2, mouse