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Science 11 April 1997:
Vol. 276. no. 5310, pp. 248 - 250
DOI: 10.1126/science.276.5310.248
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Reports

Dopamine Neuron Agenesis in Nurr1-Deficient Mice

Rolf H. Zetterström, Ludmila Solomin, Lottie Jansson, Barry J. Hoffer, Lars Olson, Thomas Perlmann *

Dopamine neurons of the substantia nigra and ventral tegmental area regulate movement and affective behavior and degenerate in Parkinson's disease. The orphan nuclear receptor Nurr1 was shown to be expressed in developing dopamine neurons before the appearance of known phenotypic markers for these cells. Mice lacking Nurr1 failed to generate midbrain dopaminergic neurons, were hypoactive, and died soon after birth. Nurr1 expression continued into adulthood, and brains of heterozygous animals, otherwise apparently healthy, contained reduced dopamine levels. These results suggest that putative Nurr1 ligands may be useful for treatment of Parkinson's disease and other disorders of midbrain dopamine circuitry.

R. H. Zetterström and L. Olson, Department of Neuroscience, Karolinska Institute, S-171 77 Stockholm, Sweden.
L. Solomin, L. Jansson, T. Perlmann, The Ludwig Institute for Cancer Research, Stockholm Branch, Post Office Box 240, S-171 77 Stockholm, Sweden.
B. J. Hoffer, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
*   To whom correspondence should be addressed. E-mail: thomas.perlmann{at}licr.ki.se

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SRC-1 Null Mice Exhibit Moderate Motor Dysfunction and Delayed Development of Cerebellar Purkinje Cells.
E. Nishihara, H. Yoshida-Komiya, C.-S. Chan, L. Liao, R. L. Davis, B. W. O'Malley, and J. Xu (2003)
J. Neurosci. 23, 213-222
   Abstract »    Full Text »    PDF »
Identification of ATF-2 as a Transcriptional Regulator for the Tyrosine Hydroxylase Gene.
T. Suzuki, T. Yamakuni, M. Hagiwara, and H. Ichinose (2002)
J. Biol. Chem. 277, 40768-40774
   Abstract »    Full Text »    PDF »
Requirements for Heterodimerization between the Orphan Nuclear Receptor Nurr1 and Retinoid X Receptors.
P. Sacchetti, H. Dwornik, P. Formstecher, C. Rachez, and P. Lefebvre (2002)
J. Biol. Chem. 277, 35088-35096
   Abstract »    Full Text »    PDF »
Defining Requirements for Heterodimerization between the Retinoid X Receptor and the Orphan Nuclear Receptor Nurr1.
P. Aarnisalo, C.-H. Kim, J. W. Lee, and T. Perlmann (2002)
J. Biol. Chem. 277, 35118-35123
   Abstract »    Full Text »    PDF »
Minireview: Genomics Versus Orphan Nuclear Receptors--A Half-Time Report.
T. M. Willson and J. T. Moore (2002)
Mol. Endocrinol. 16, 1135-1144
   Abstract »    Full Text »    PDF »
Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers.
M. J. Bannon, B. Pruetz, A. B. Manning-Bog, C. J. Whitty, S. K. Michelhaugh, P. Sacchetti, J. G. Granneman, D. C. Mash, and C. J. Schmidt (2002)
PNAS 99, 6382-6385
   Abstract »    Full Text »    PDF »
Association of homozygous 7048G7049 variant in the intron six of Nurr1 gene with Parkinson's disease.
P.-Y. Xu, R. Liang, J. Jankovic, C. Hunter, Y.-X. Zeng, T. Ashizawa, D. Lai, and W.-D. Le (2002)
Neurology 58, 881-884
   Abstract »    Full Text »    PDF »
Dopamine as a Prolactin (PRL) Inhibitor.
N. Ben-Jonathan and R. Hnasko (2001)
Endocr. Rev. 22, 724-763
   Abstract »    Full Text »    PDF »
Induction of Cell Cycle Arrest and Morphological Differentiation by Nurr1 and Retinoids in Dopamine MN9D Cells.
D. S. Castro, E. Hermanson, B. Joseph, A. Wallen, P. Aarnisalo, A. Heller, and T. Perlmann (2001)
J. Biol. Chem. 276, 43277-43284
   Abstract »    Full Text »    PDF »
Phenotypic Differentiation during Migration of Dopaminergic Progenitor Cells to the Olfactory Bulb.
H. Baker, N. Liu, H. S. Chun, S. Saino, R. Berlin, B. Volpe, and J. H. Son (2001)
J. Neurosci. 21, 8505-8513
   Abstract »    Full Text »    PDF »
Fate of Midbrain Dopaminergic Neurons Controlled by the Engrailed Genes.
H. H. Simon, H. Saueressig, W. Wurst, M. D. Goulding, and D. D. M. O'Leary (2001)
J. Neurosci. 21, 3126-3134
   Abstract »    Full Text »    PDF »
Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety.
C. Labarca, J. Schwarz, P. Deshpande, S. Schwarz, M. W. Nowak, C. Fonck, R. Nashmi, P. Kofuji, H. Dang, W. Shi, et al. (2001)
PNAS
   Abstract »    Full Text »
Parathyroid Hormone Induces Expression of the Nuclear Orphan Receptor Nurr1 in Bone Cells.
S. Tetradis, O. Bezouglaia, and A. Tsingotjidou (2001)
Endocrinology 142, 663-670
   Abstract »    Full Text »    PDF »
Dopamine-Deficient Mice Are Hypersensitive to Dopamine Receptor Agonists.
D. S. Kim, M. S. Szczypka, and R. D. Palmiter (2000)
J. Neurosci. 20, 4405-4413
   Abstract »    Full Text »    PDF »
Rational discovery of novel nuclear hormone receptor antagonists.
M. Schapira, B. M. Raaka, H. H. Samuels, and R. Abagyan (2000)
PNAS 97, 1008-1013
   Abstract »    Full Text »    PDF »
Increased cell death and delayed development in the cerebellum of mice lacking the rev-erbA(alpha) orphan receptor.
P Chomez, I Neveu, A Mansen, E Kiesler, L Larsson, B Vennstrom, and E Arenas (2000)
Development 127, 1489-1498
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Activity of the Nurr1 Carboxyl-terminal Domain Depends on Cell Type and Integrity of the Activation Function 2.
D. S. Castro, M. Arvidsson, M. B. Bolin, and T. Perlmann (1999)
J. Biol. Chem. 274, 37483-37490
   Abstract »    Full Text »    PDF »
The ETS Domain Factor Pet-1 Is an Early and Precise Marker of Central Serotonin Neurons and Interacts with a Conserved Element in Serotonergic Genes.
T. Hendricks, N. Francis, D. Fyodorov, and E. S. Deneris (1999)
J. Neurosci. 19, 10348-10356
   Abstract »    Full Text »    PDF »
Heterodimerization between Members of the Nur Subfamily of Orphan Nuclear Receptors as a Novel Mechanism for Gene Activation.
M. Maira, C. Martens, A. Philips, and J. Drouin (1999)
Mol. Cell. Biol. 19, 7549-7557
   Abstract »    Full Text »    PDF »


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