Sci. Aging Knowl. Environ., 20 April 2005
Vol. 2005, Issue 16, p. tg3
GENETICALLY ALTERED MICE
||129/Ola (embryonic stem cells), C57BL/6 (blastocysts)
||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.
||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.
||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).
||These mice are not commercially available. Please contact:
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
||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.
||Mouse Gene Informatics:
Online Mendelian Inheritance in Man:
April 20, 2005
- 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]
- 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]
- 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]
- 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]
Mice. Sci. Aging Knowl. Environ. 2005
(16), tg3 (2005).