Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
2006-05-02
2006-05-02
Myers, Carla J. (Department: 1634)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S091200, C536S023100, C536S023500
Reexamination Certificate
active
07037657
ABSTRACT:
The identification of mutations in NURR1 provides molecular tools for the development of diagnostic, prophylactic and therapeutic agents for Parkinson's Disease. In specific embodiments, two point mutations are identified in exon 1 of the NURR1 gene in 10/107 (9.3%) cases of familial Parkinson's disease (PD). The mutations reduce NURR1 gene expression (mRNA and protein levels) by 87–95% and decrease tyrosine hydroxylase (a rate-limited dopamine synthesis enzyme) gene expression in vitro. It is also demonstrated that in vivo NURR1 mRNA levels in the lymphocytes from the PD patients with the exon 1 mutation are reduced by 68–84%, and in over 50% sporadic PD patients the NURR1 mRNA levels in lymphocytes are significantly reduced. A homozygous polymorphism is identified in intron 6 of NURR1 that correlates with the presence of Parkinson's disease. A splicing variant in NURR1 exon 5 is identified.
REFERENCES:
patent: 6284539 (2001-09-01), Bowen et al.
patent: 6312949 (2001-11-01), Sakurada et al.
patent: 6395546 (2002-05-01), Zobel et al.
Mages et al. Molecular Endocrinology. 1994. 8: 1583-1591.
McEvoy et al. The Journal of Immunology. 2002. 168: 2979-2987.
Nichols et al. Movement Disorders. 2004 19: 649-655.
Tan et al. Neuroscience Letters. 2003. 347: 139-142.
Nichols et al. Neurology. Mar. 2003. 60: A281-282.
Le, Wei-dong, et al.; Mutations in NR4A2 associated with familial Parkinson disease; Nature Genetics 33:85-89, Jan. 2003.
Le, W., et al.; Corrigendum—Mutations in NR4A2 associated with familial Parkinson disease; Nat. Genet. 33:214, Feb. 2003.
Zetterstrom, Rolf H., et al.; Dopamine Neuron Agenesis in Nurr1-Deficient Mice; Science 276:248-250, Apr. 11, 1997.
Zetterstrom, Rolf H., et al.; Cellular expression of the immediate early transcription factors Nurr1 and NGFI-B suggests a gene regulatory role in several brain regions including the nigrostriatal dopamine system; Molecular Brain Research 41:111-120, 1996.
Wallen, Asa, et al.; Fate of Mesencephalic AHD2—Expressing Dopamine Progenitor Cells in Nurr1 Mutant Mice; Experimental Cell Research 253:737-746, 1999.
Torii, T., et al.; Organization of the human orphan nuclear receptor Nurr1 gene; Gene 230:255-232. 1999.
Saucedo-Cardenas, Odila, et al.; Comparative Distribution of NURR1 and NUR77 Nuclear Receptors in the Mouse Central Nervous System; Journal of Molecular Neuroscience; 7:51-63, 1996.
Saucedo-Cardenas, Odila, et al.; Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons; Proc. Natl. Acad. Sci. USA (Neurobiology) 95:4013-4018, Mar. 1998.
Sakurada, Kazuhiro, et al.; Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain; Development 126:4017-4026, 1999.
Sacchetti, Paola, et al.; Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism; Journal of Neurochemistry 76:1565-1572, 2001.
Le, Wei-dong, et al.; Reduced Nurr1 Expression Incresases the Vulnerability of Mesencephalic Dopamine Neurons to MPTP-Induced Injury; J Neurochem. 73:2218-2221, 1999.
Le, Wei-dong, et al.; Selective Agenesis of Mesencephalic Dopaminergic Neurons in Nurr1-Deficient Mice; Experimental Neurology 159:451-458, 1999.
Castillo, Susan O., et al.; Organization, Sequence, Chromosomal Localization, and Promoter Identification of the Mouse Orphan Nuclear Receptor Nurr1 Gene; Genomics 41:250-257, 1997.
Buervenich, Silvia, et al.; Brief Research Communicatin—NURR1 Mutations in Cases of Schizophrenia and Manic-depressive Disorder; American Journal of Medical Genetics (Neuropsychiatric Genetics) 96:808-813, 2000.
Ichinose, Hiroshi, et al.; Molecular cloning of the human Nurr1 gene: characterization of the human gene and cDNAs; Gene 230:233-239, 1999.
Le, Wei-dong, et al.; Polymorphism at Intron 6 of Nurr1 Gene Is Associated with Familial Parkinson Disease; Neurology 56(3):A120, Apr. 2001.
Le Wei-Dong
Vassilatis Demetrios K.
Baylor College of Medicine
Fulbright & Jaworski LLP
Myers Carla J.
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