Mammalian Genome

, Volume 15, Issue 3, pp 210–217 | Cite as

The neurological mutant quakingviable is Parkin deficient

  • Diego Lorenzetti
  • Barbara Antalffy
  • Hannes Vogel
  • Janice Noveroske
  • Dawna Armstrong
  • Monica Justice
Original Contribution

Abstract

The mouse mutant quakingviable (qkv) has been studied for almost four decades as a model for dysmyelination of the central nervous system (CNS). The genetic lesion associated with the qkv phenotype is a large deletion of approximately 1 Megabase on mouse Chromosome (Chr) 17. This deficiency alters the expression of transcripts from the qkI locus in oligodendrocytes, resulting in improper myelination of the CNS in animals homozygous for the deletion. To determine whether other genes within the deletion contribute to the quakingviable phenotype, we physically mapped and sequenced the deleted interval. We determined that the mouse Parkin gene, as well as the Parkin co-regulated gene (Pacrg), lies within the qkv deletion. We determined that qkv mutants completely lack the expression of the Parkin gene product. Loss-of-function mutations in the human PARKIN gene cause autosomal juvenile Parkinson’s disease (AR-JP). Our studies show that the deletion of Parkin in qkv brains does not result in the loss of dopaminergic neurons typical of AR-JP patients. Also, α-synuclein, a target of Parkin-dependent ubiquitination, does not accumulate in qkv mutant brains. Despite the lack of AR-JP-like neuropathology in qkv mice, this mutant may constitute a readily available model for the study of the cellular function of Parkin. This is the first report of a gene distinct from qkI affected by the qkv deletion. The discovery of the multigenic nature of this classical mouse mutation calls for the re-evaluation of its phenotypic characterization.

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Copyright information

© Springer-Verlag New York Inc. 2004

Authors and Affiliations

  • Diego Lorenzetti
    • 1
  • Barbara Antalffy
    • 2
  • Hannes Vogel
    • 3
  • Janice Noveroske
    • 4
  • Dawna Armstrong
    • 2
  • Monica Justice
    • 1
  1. 1.Department of Molecular and Human GeneticsBaylor College of Medicine, One Baylor Plaza, Room S413, Houston, Texas 77030USA
  2. 2.Department of PathologyBaylor College of Medicine, Houston, TexasUSA
  3. 3.Department of PathologyStanford University School of Medicine, Palo Alto, CaliforniaUSA
  4. 4.The Jackson LaboratoryBar Harbor, MaineUSA

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