Sci. Aging Knowl. Environ., 20 April 2005
Vol. 2005, Issue 16, p. tg3
[DOI: 10.1126/sageke.2005.16.tg3]

GENETICALLY ALTERED MICE

DJ-1–/– Mice

http://sageke.sciencemag.org/cgi/content/full/2005/16/tg3


Mouse DJ-1–/– mice
Genetic background 129/Ola (embryonic stem cells), C57BL/6 (blastocysts)
Gene changed DJ-1; also called Dj1, Parkinson disease (autosomal recessive, early onset) 7, and Park7
Type of change Targeted deletion of DJ-1 exons 3 to 5 was achieved by homologous recombination.
Nature of protein DJ-1 is a ubiquitous, highly conserved protein of unknown function. However, there is evidence suggesting that it is involved in the oxidative stress response (see Giasson Perspective) and that loss of DJ-1 function leads to neurodegeneration.
Phenotype DJ-1–/– mice are viable and fertile and demonstrate no gross anatomical or neuronal abnormalities, indicating that loss of DJ-1 alone is not sufficient to produce symptoms of Parkinson's disease (PD). However, DJ-1–/– mice display hypersensitivity to methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP, an inhibitor of mitochondrial complex I; see Andersen Review) as compared with wild-type controls. With treatment with MPTP, DJ-1–/– mice develop PD-like symptoms. The striatal denervation in MPTP-treated DJ-1–/– mice resembles the substantia nigra pars compacta neuronal loss observed in human PD patients.
Corresponding human phenotype PARK7 gene mutations result in the onset of PD pathologies, including rigidity, bradykinesia, and tremor, before the age of 40 years. Many patients with PARK7 mutations also present with psychiatric symptoms.
See Constantino Case Study for a description of a patient with PD.
Primary reference R. H. Kim, P. D. Smith, H. Aleyasin, S. Hayley, M. P. Mount, S. Pownall, A. Wakeham, A. J. You-Ten, S. Kalia, P. Home et al., Hypersensitivity of DJ-1 deficient mice to methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc. Natl. Acad. Sci. U.S.A. 102, 5215-5220 (2005).
Additional references See below.
Source These mice are not commercially available. Please contact:
Tak Mak
Campbell Family Institute for Breast Cancer Research
Advanced Medical Discovery Institute
Ontario Cancer Institute and Department of Medical Biophysics
University of Toronto
Toronto, ON, Canada M5G 2C1
E-mail: tmak@uhnres.utoronto.ca
Other comments Primary cortical neurons derived from DJ-1–/– embryos display hypersensitivity to oxidative (but not nonoxidative) stress. Furthermore, overproduction of DJ-1 in primary cortical neurons from wild-type mice increases resistance to oxidative stress; overproduction in the striatum of wild-type mice increases resistance to striatal damage caused by MPTP.
Other links Mouse Gene Informatics:
Park7
Online Mendelian Inheritance in Man:
ONCOGENE DJ1
Keywords Parkinson's disease
oxidative stress
MPTP
Prepared by Jennifer Fuller


April 20, 2005
  1. V. Bonifati, P. Rizzu, M. J. van Baren, O. Schaap, G. J. Breedveld, E. Krieger, M. C. Dekker, F. Squitieri, P. Ibanez, M. Joosse et al., Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299, 256-259 (2003).[Abstract/Free Full Text]
  2. R. H. Kim, P. D. Smith, H. Aleyasin, S. Hayley, M. P. Mount, S. Pownall, A. Wakeham, A. J. You-Ten, S. Kalia, P. Home et al., Hypersensitivity of DJ-1 deficient mice to methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc. Natl. Acad. Sci. U.S.A. 102, 5215-5220 (2005).[Abstract/Free Full Text]
  3. D. Nagakubo, T. Taira, H. Kitaura, M. Ikeda, K. Tamai, S. M. Iguchi-Ariga, H. Ariga, DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras. Biochem. Biophys. Res. Commun. 231, 509-513 (1997).[CrossRef][Medline]
  4. T. Taira, K. Takahashi, R. Kitagawa, S. M. Iguchi-Ariga, H. Ariga, Molecular cloning of human and mouse DJ-1 genes and identification of Sp1-dependent activation of the human DJ-1 promoter. Gene 263, 285-292 (2001).[CrossRef][Medline]
Citation: DJ-1–/– Mice. Sci. Aging Knowl. Environ. 2005 (16), tg3 (2005).








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