Human Molecular Genetics Advance Access published online on July 22, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg239
© 2003 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Functional Genomics Department, Aventis Pharma S.A., 13 Quai Jules Guesde, F-94400 Vitry-sur-Seine, France
* To whom correspondence should be addressed. E-mail: thomas.rooney{at}aventis.com.
Mutations of the parkin gene are the most frequent cause of early onset-autosomal recessive parkinsonism (EO-AR). Here we show that inactivation of the parkin gene in mice results in motor and cognitive deficits, inhibition of amphetamine-induced dopamine release and inhibition of glutamate neurotransmission. The levels of dopamine are increased in the limbic brain areas of parkin mutant mice and there is a shift towards increased metabolism of dopamine by MAO. Although there was no evidence for a reduction of nigrostriatal dopamine neurons in the parkin mutant mice, the level of dopamine transporter protein was reduced in these animals, suggesting a decreased density of dopamine terminals, or adaptative changes in the nigrostriatal dopamine system. GSH levels were increased in the striatum and fetal mesencephalic neurons from parkin mutant mice, suggesting that a compensatory mechanism may protect dopamine neurons from neuronal death. These parkin mutant mice provide a valuable tool to better understand the preclinical deficits observed in patients with PD and to characterize the mechanisms leading to the degeneration of dopamine neurons that could provide new strategies for neuroprotection.
Article
Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse
2 INSERM U289, Groupe Hopitalier Pitié-Salpêtrière, 47, Bd de l'Hôpital, 75651 Paris Cedex 13, France
3 Department of Research, Hospital Ramon y Cajal, Carretera de Colmenar km. 9,100, 28034 - Madrid, Spain
4 CNRS UMR 7593, Hopitalier Pitié-Salpêtrière, 47, Bd de l'Hôpital, 75651 Paris Cedex 13, France
5 CNS Department, Aventis Pharma S.A., 13 Quai Jules Guesde, F-94400 Vitry-sur-Seine, France
6 Department of Neurology, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Avda. de Reyes Católicos, 2. 28040 - Madrid, Spain
7 INSERM U289, Groupe Hopitalier Pitié-Salpêtrière, 47, Bd de l'Hôpital, 75651 Paris Cedex 13, France; Département de Génétique, Cytogénétique et Embryologie, Groupe Hopitalier Pitié-Salpêtrière, AP-HP, 47, Bd de l'Hôpital, 75651 Paris Cedex 13, France
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. P. Hart and A. Xu Mice Expressing Mutant Parkin Exhibit Hallmark Features of Parkinson's Disease J. Neurosci., June 10, 2009; 29(23): 7392 - 7394. [Full Text] [PDF]
|
|
|
|
|
|
X.-H. Lu, S. M. Fleming, B. Meurers, L. C. Ackerson, F. Mortazavi, V. Lo, D. Hernandez, D. Sulzer, G. R. Jackson, N. T. Maidment, et al. Bacterial Artificial Chromosome Transgenic Mice Expressing a Truncated Mutant Parkin Exhibit Age-Dependent Hypokinetic Motor Deficits, Dopaminergic Neuron Degeneration, and Accumulation of Proteinase K-Resistant {alpha}-Synuclein J. Neurosci., February 18, 2009; 29(7): 1962 - 1976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Helton, T. Otsuka, M.-C. Lee, Y. Mu, and M. D. Ehlers Pruning and loss of excitatory synapses by the parkin ubiquitin ligase PNAS, December 9, 2008; 105(49): 19492 - 19497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Mena and J. Garcia de Yebenes Glial Cells as Players in Parkinsonism: The "Good," the "Bad," and the "Mysterious" Glia Neuroscientist, December 1, 2008; 14(6): 544 - 560. [Abstract] [PDF]
|
|
|
|
|
|
T. C. Frank-Cannon, T. Tran, K. A. Ruhn, T. N. Martinez, J. Hong, M. Marvin, M. Hartley, I. Trevino, D. E. O'Brien, B. Casey, et al. Parkin Deficiency Increases Vulnerability to Inflammation-Related Nigral Degeneration J. Neurosci., October 22, 2008; 28(43): 10825 - 10834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Rodriguez-Navarro, A. Gomez, I. Rodal, J. Perucho, A. Martinez, V. Furio, I. Ampuero, M. J. Casarejos, R. M. Solano, J. G. de Yebenes, et al. Parkin deletion causes cerebral and systemic amyloidosis in human mutated tau over-expressing mice Hum. Mol. Genet., October 15, 2008; 17(20): 3128 - 3143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Solano, M. J. Casarejos, J. Menendez-Cuervo, J. A. Rodriguez-Navarro, J. Garcia de Yebenes, and M. A. Mena Glial Dysfunction in Parkin Null Mice: Effects of Aging J. Neurosci., January 16, 2008; 28(3): 598 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Cookson, W. Dauer, T. Dawson, E. A. Fon, M. Guo, and J. Shen The Roles of Kinases in Familial Parkinson's Disease J. Neurosci., October 31, 2007; 27(44): 11865 - 11868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Stichel, X.-R. Zhu, V. Bader, B. Linnartz, S. Schmidt, and H. Lubbert Mono- and double-mutant mouse models of Parkinson's disease display severe mitochondrial damage Hum. Mol. Genet., October 15, 2007; 16(20): 2377 - 2393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Joch, A. R. Ase, C. X.-Q. Chen, P. A. MacDonald, M. Kontogiannea, A. T. Corera, A. Brice, P. Seguela, and E. A. Fon Parkin-mediated Monoubiquitination of the PDZ Protein PICK1 Regulates the Activity of Acid-sensing Ion Channels Mol. Biol. Cell, August 1, 2007; 18(8): 3105 - 3118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kitada, A. Pisani, D. R. Porter, H. Yamaguchi, A. Tscherter, G. Martella, P. Bonsi, C. Zhang, E. N. Pothos, and J. Shen From the Cover: Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice PNAS, July 3, 2007; 104(27): 11441 - 11446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Mandemakers, V. A. Morais, and B. De Strooper A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases J. Cell Sci., May 15, 2007; 120(10): 1707 - 1716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hatano, S.-i. Kubo, S. Imai, M. Maeda, K. Ishikawa, Y. Mizuno, and N. Hattori Leucine-rich repeat kinase 2 associates with lipid rafts Hum. Mol. Genet., March 15, 2007; 16(6): 678 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Yi and M. D. Ehlers Emerging Roles for Ubiquitin and Protein Degradation in Neuronal Function Pharmacol. Rev., March 1, 2007; 59(1): 14 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kitao, Y. Imai, K. Ozawa, A. Kataoka, T. Ikeda, M. Soda, K. Nakimawa, H. Kiyama, D. M. Stern, O. Hori, et al. Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation Hum. Mol. Genet., January 1, 2007; 16(1): 50 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Menendez, J.A. Rodriguez-Navarro, R.M. Solano, M.J. Casarejos, I. Rodal, R. Guerrero, M.P. Sanchez, J. Avila, M.A. Mena, and J.G. de Yebenes Suppression of Parkin enhances nigrostriatal and motor neuron lesion in mice over-expressing human-mutated tau protein Hum. Mol. Genet., July 1, 2006; 15(13): 2045 - 2058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Escalier Knockout mouse models of sperm flagellum anomalies Hum. Reprod. Update, July 1, 2006; 12(4): 449 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Jenner and C. W. Olanow The pathogenesis of cell death in Parkinson's disease Neurology, May 23, 2006; 66(10_suppl_4): S24 - S36. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. Jiang, Q. Jiang, W. Liu, and J. Feng Parkin Suppresses the Expression of Monoamine Oxidases J. Biol. Chem., March 31, 2006; 281(13): 8591 - 8599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A.F. Marteijn, L. van Emst, C. A.J. Erpelinck-Verschueren, G. Nikoloski, A. Menke, T. de Witte, B. Lowenberg, J. H. Jansen, and B. A. van der Reijden The E3 ubiquitin-protein ligase Triad1 inhibits clonogenic growth of primary myeloid progenitor cells Blood, December 15, 2005; 106(13): 4114 - 4123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Springer, T. Hoppe, E. Schmidt, and R. Baumeister A Caenorhabditis elegans Parkin mutant with altered solubility couples {alpha}-synuclein aggregation to proteotoxic stress Hum. Mol. Genet., November 15, 2005; 14(22): 3407 - 3423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. O'Brien, G. S. Johnson, R. D. Schnabel, S. Khan, J. R. Coates, G. C. Johnson, and J. F. Taylor Genetic Mapping of Canine Multiple System Degeneration and Ectodermal Dysplasia Loci J. Hered., November 1, 2005; 96(7): 727 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Sriram, X. Li, H. S. Ko, K. K.K. Chung, E. Wong, K. L. Lim, V. L. Dawson, and T. M. Dawson Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin Hum. Mol. Genet., September 1, 2005; 14(17): 2571 - 2586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Ko, R. von Coelln, S. R. Sriram, S. W. Kim, K. K. K. Chung, O. Pletnikova, J. Troncoso, B. Johnson, R. Saffary, E. L. Goh, et al. Accumulation of the Authentic Parkin Substrate Aminoacyl-tRNA Synthetase Cofactor, p38/JTV-1, Leads to Catecholaminergic Cell Death J. Neurosci., August 31, 2005; 25(35): 7968 - 7978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhong, Y. Tan, A. Zhou, Q. Yu, and J. Zhou RING Finger Ubiquitin-Protein Isopeptide Ligase Nrdp1/FLRF Regulates Parkin Stability and Activity J. Biol. Chem., March 11, 2005; 280(10): 9425 - 9430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Perez and R. D. Palmiter Parkin-deficient mice are not a robust model of parkinsonism PNAS, February 8, 2005; 102(6): 2174 - 2179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jiang, Q. Jiang, and J. Feng Parkin Increases Dopamine Uptake by Enhancing the Cell Surface Expression of Dopamine Transporter J. Biol. Chem., December 24, 2004; 279(52): 54380 - 54386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jiang, Y. Ren, J. Zhao, and J. Feng Parkin protects human dopaminergic neuroblastoma cells against dopamine-induced apoptosis Hum. Mol. Genet., August 15, 2004; 13(16): 1745 - 1754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. von Coelln, B. Thomas, J. M. Savitt, K. L. Lim, M. Sasaki, E. J. Hess, V. L. Dawson, and T. M. Dawson Loss of locus coeruleus neurons and reduced startle in parkin null mice PNAS, July 20, 2004; 101(29): 10744 - 10749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Marazziti, E. Golini, S. Mandillo, A. Magrelli, W. Witke, R. Matteoni, and G. P. Tocchini-Valentini Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor PNAS, July 6, 2004; 101(27): 10189 - 10194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lorenzetti, C. E. Bishop, and M. J. Justice Deletion of the Parkin coregulated gene causes male sterility in the quakingviable mouse mutant PNAS, June 1, 2004; 101(22): 8402 - 8407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Marin, J. I. Lucas, A.-C. Gradilla, and A. Ferrus Parkin and relatives: the RBR family of ubiquitin ligases Physiol Genomics, May 19, 2004; 17(3): 253 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Pesah, T. Pham, H. Burgess, B. Middlebrooks, P. Verstreken, Y. Zhou, M. Harding, H. Bellen, and G. Mardon Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress Development, May 1, 2004; 131(9): 2183 - 2194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Palacino, D. Sagi, M. S. Goldberg, S. Krauss, C. Motz, M. Wacker, J. Klose, and J. Shen Mitochondrial Dysfunction and Oxidative Damage in parkin-deficient Mice J. Biol. Chem., April 30, 2004; 279(18): 18614 - 18622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. F. Mata, P. J. Lockhart, and M. J. Farrer Parkin genetics: one model for Parkinson's disease Hum. Mol. Genet., April 1, 2004; 13(90001): R127 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Baptista, M. R. Cookson, and D. W. Miller Parkin and {alpha}-Synuclein: Opponent Actions in The Pathogenesis of Parkinson'S Disease Neuroscientist, February 1, 2004; 10(1): 63 - 72. [Abstract] [PDF]
|
|