Neurons Expressing the Highest Levels of γ-Synuclein Are Unaffected by Targeted Inactivation of the Gene

REFERENCES

• Abeliovich, A., Y. Schmitz, I. Farinas, D. Choi-Lundberg, W. H. Ho, P. E. Castillo, N. Shinsky, J. M. Verdugo, M. Armanini, A. Ryan, M. Hynes, H. Phillips, D. Sulzer, and A. Rosenthal. 2000. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25: 239–252.
   PubMed Web of Science ®Google Scholar
• Alimova-Kost, M. V., N. N. Ninkina, S. Imreh, N. V. Gnuchev, J. Adu, A. M. Davies, and V. L. Buchman. 1999. Genomic structure and chromosomal localization of the mouse persyn gene. Genomics 56: 224–227.
   PubMedGoogle Scholar
• Bennett, G. L., and Y.-K. Xie. 1988. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33: 87–109.
   PubMed Web of Science ®Google Scholar
• Biere, A. L., S. J. Wood, J. Wypych, S. Steavenson, Y. Jiang, D. Anafi, F. W. Jacobsen, M. A. Jarosinski, G. M. Wu, J. C. Louis, F. Martin, L. O. Narhi, and M. Citron. 2000. Parkinson's disease-associated alpha-synuclein is more fibrillogenic than beta- and gamma-synuclein and cannot cross-seed its homologs. J. Biol. Chem. 275: 34574–34579.
   PubMed Web of Science ®Google Scholar
• Blackburn-Munro, G., and S. M. Fleetwood-Walker. 1999. The sodium channel auxiliary subunits beta1 and beta2 are differentially expressed in the spinal cord of neuropathic rats. Neuroscience 90: 153–164.
   PubMed Web of Science ®Google Scholar
• Buchman, V. L., J. Adu, L. G. P. Pinõn, N. N. Ninkina, and A. M. Davies. 1998. Persyn, a member of the synuclein family, influences neurofilament network integrity. Nat. Neurosci. 1: 101–103.
   PubMed Web of Science ®Google Scholar
• Buchman, V. L., H. J. A. Hunter, L. G. P. Pinõn, J. Thompson, E. M. Privalova, N. N. Ninkina, and A. M. Davies. 1998. Persyn, a member of the synuclein family, has a distinct pattern of expression in the developing nervous system. J. Neurosci. 18: 9335–9341.
   PubMed Web of Science ®Google Scholar
• Cabin, D. E., K. Shimazu, D. Murphy, N. B. Cole, W. Gottschalk, K. L. McIlwain, B. Orrison, A. Chen, C. E. Ellis, R. Paylor, B. Lu, and R. L. Nussbaum. 2002. Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking α-synuclein. J. Neurosci. 22: 8797–8807.
   PubMed Web of Science ®Google Scholar
• Coggeshall, R. E., P. M. Dougherty, C. M. Pover, and S. M. Carlton. 1993. Is large myelinated fiber loss associated with hyperalgesia in a model of experimental peripheral neuropathy in the rat? Pain 52: 233–242.
   PubMed Web of Science ®Google Scholar
• Dev, K. K., K. Hofele, S. Barbieri, V. L. Buchman, and H. van der Putten. 2003. α-Synuclein and its molecular pathophysiological role in neurodegenerative disease. Neuropharmacology 45: 14–44.
   PubMedGoogle Scholar
• Dickinson, T., R. Mitchell, P. Robberecht, and S. M. Fleetwood-Walker. 1999. The role of VIP/PACAP receptor subtypes in spinal somatosensory processing in rats with an experimental peripheral mononeuropathy. Neuropharmacology 38: 167–180.
   PubMedGoogle Scholar
• Dickson, D. W. 2001. Alpha-synuclein and the Lewy body disorders. Curr. Opin. Neurol. 14: 423–432.
   PubMedGoogle Scholar
• Eliezer, D., E. Kutluay, R. Bussell, Jr., and G. Browne. 2001. Conformational properties of alpha-synuclein in its free and lipid-associated states. J. Mol. Biol. 307: 1061–1073.
   PubMed Web of Science ®Google Scholar
• Filliatreau, G., N. Attal, R. Hassig, G. Guilbaud, J. Desmeules, and L. DiGiamberardino. 1994. Time-course of nociceptive disorders induced by chronic loose ligatures of the rat sciatic nerve and changes of the acetylcholinesterase transport along the ligated nerve. Pain 59: 405–413.
   PubMedGoogle Scholar
• Galvin, J. E., B. Giasson, H. I. Hurtig, V. M. Lee, and J. Q. Trojanowski. 2000. Neurodegeneration with brain iron accumulation, type 1 is characterized by alpha-, beta-, and gamma-synuclein neuropathology. Am. J. Pathol. 157: 361–368.
   PubMed Web of Science ®Google Scholar
• Galvin, J. E., V. M. Lee, and J. Q. Trojanowski. 2001. Synucleinopathies: clinical and pathological implications. Arch. Neurol. 58: 186–190.
   PubMed Web of Science ®Google Scholar
• Galvin, J. E., K. Uryu, V. M. Lee, and J. Q. Trojanowski. 1999. Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains alpha-, beta-, and gamma-synuclein. Proc. Natl. Acad. Sci. USA 96: 13450–13455.
   PubMedGoogle Scholar
• Giasson, B. I., J. E. Duda, M. S. Forman, V. M. Lee, and J. Q. Trojanowski. 2001. Prominent perikaryal expression of alpha- and beta-synuclein in neurons of dorsal root ganglion and in medullary neurons. Exp. Neurol. 172: 354–362.
   PubMed Web of Science ®Google Scholar
• Giasson, B. I., J. E. Duda, S. M. Quinn, B. Zhang, J. Q. Trojanowski, and V. M. Lee. 2002. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34: 521–533.
   PubMed Web of Science ®Google Scholar
• Goedert, M. 2001. Alpha-synuclein and neurodegenerative diseases. Nat. Rev. Neurosci. 2: 492–501.
   PubMed Web of Science ®Google Scholar
• Guilbaud, G., M. Gautron, F. Jazat, H. Ratinahirana, R. Hassig, and J. J. Hauw. 1993. Time course of degeneration and regeneration of myelinated nerve fibres following chronic loose ligatures of the rat sciatic nerve: can nerve lesions be linked to the abnormal pain-related behaviours? Pain 53: 147–158.
   PubMed Web of Science ®Google Scholar
• Gundersen, H. J. G. 1986. Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in the memory of William R. Thompson. J. Microsc. 143: 3–45.
   Google Scholar
• Hashimoto, M., E. Rockenstein, M. Mante, M. Mallory, and E. Masliah. 2001. Beta-synuclein inhibits alpha-synuclein aggregation. A possible role as an anti-parkinsonian factor. Neuron 32: 213–223.
   PubMed Web of Science ®Google Scholar
• Jakes, R., M. G. Spillantini, and M. Goedert. 1994. Identification of two distinct synucleins from human brain. FEBS Lett. 345: 27–32.
   PubMed Web of Science ®Google Scholar
• Jensen, P. H., J. Y. Li, A. Dahlstrom, and C. G. Dotti. 1999. Axonal transport of synucleins is mediated by all rate components. Eur. J. Neurosci. 11: 3369–3376.
   PubMedGoogle Scholar
• Ji, H., Y. E. Liu, T. Jia, M. Wang, J. Liu, G. Xiao, B. K. Joseph, C. Rosen, and Y. E. Shi. 1997. Identification of a breast cancer-specific gene, BCSG1, by direct differential cDNA sequencing. Cancer Res. 57: 759–764.
   PubMed Web of Science ®Google Scholar
• Konigsmark, B. W. 1970. Methods for the counting of neurons, p. 315–340. In W. J. H. Nauta and S. O. E. Ebbesson (ed.), Contemporary research methods in neuroanatomy. Springer-Verlag, Berlin, Germany.
   Google Scholar
• Kruger, R., O. Eberhardt, O. Riess, and J. B. Schulz. 2002. Parkinson's disease: one biochemical pathway to fit all genes? Trends Mol. Med. 8: 236–240.
   PubMedGoogle Scholar
• Lavedan, C., E. Leroy, A. Dehejia, S. Buchholtz, A. Dutra, R. L. Nissbaum, and M. H. Polymeropoulos. 1998. Identification, localization and characterization of the human γ-synuclein gene. Hum. Genet. 103: 106–112.
   PubMedGoogle Scholar
• Lee, M. K., W. Stirling, Y. Xu, X. Xu, D. Qui, A. S. Mandir, T. M. Dawson, N. G. Copeland, N. A. Jenkins, and D. L. Price. 2002. Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53→Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice. Proc. Natl. Acad. Sci. USA 99: 8968–8973.
   PubMed Web of Science ®Google Scholar
• Lesuisse, C., and L. J. Martin. 2002. Long-term culture of mouse cortical neurons as a model for neuronal development, aging, and death. J. Neurobiol. 51: 9–23.
   PubMedGoogle Scholar
• Li, J.-Y., P. H. Jensen, and A. Dahlstrüm. 2002. Differential localization of α-, β- and γ-synucleins in the rat CNS. Neuroscience 113: 463–478.
   PubMed Web of Science ®Google Scholar
• Lotharius, J., and P. Brundin. 2002. Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein. Nat. Rev. Neurosci. 3: 932–942.
   PubMed Web of Science ®Google Scholar
• McNaught, K. S., and C. W. Olanow. 2003. Proteolytic stress: a unifying concept for the etiopathogenesis of Parkinson's disease. Ann. Neurol. 53: S73–S84.
   PubMedGoogle Scholar
• Nakajo, S., K. Tsukada, K. Omata, Y. Nakamura, and K. Nakaya. 1993. A new brain-specific 14-kDa protein is a phosphoprotein. Its complete amino acid sequence and evidence for phosphorylation. Eur. J. Biochem. 217: 1057–1063.
   PubMedGoogle Scholar
• Ninkina, N. N., M. V. Alimova-Kost, J. W. E. Paterson, L. Delaney, B. B. Cohen, S. Imreh, N. V. Gnuchev, A. M. Davies, and V. L. Buchman. 1998. Organisation, expression and polymorphism of the human persyn gene. Hum. Mol. Genet. 7: 1417–1424.
   PubMed Web of Science ®Google Scholar
• Ostrerova, N., L. Petrucelli, M. Farrer, N. Mehta, P. Choi, J. Hardy, and B. Wolozin. 1999. Alpha-synuclein shares physical and functional homology with 14-3-3 proteins. J. Neurosci. 19: 5782–5791.
   PubMed Web of Science ®Google Scholar
• Ostrerova-Golts, N., L. Petrucelli, J. Hardy, J. M. Lee, M. Farrer, and B. Wolozin. 2000. The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. J. Neurosci. 20: 6048–6054.
   PubMed Web of Science ®Google Scholar
• Pan, Z. Z., W. Bruening, B. I. Giasson, V. M. Lee, and A. K. Godwin. 2002. Gamma-synuclein promotes cancer cell survival and inhibits stress- and chemotherapy drug-induced apoptosis by modulating MAPK pathways. J. Biol. Chem. 277: 35050–35060.
   PubMedGoogle Scholar
• Park, J. Y., and P. T. Lansbury, Jr. 2003. Beta-synuclein inhibits formation of alpha-synuclein protofibrils: a possible therapeutic strategy against Parkinson's disease. Biochemistry 42: 3696–3700.
   PubMed Web of Science ®Google Scholar
• Petrucelli, L., C. O'Farrell, P. J. Lockhart, M. Baptista, K. Kehoe, L. Vink, P. Choi, B. Wolozin, M. Farrer, J. Hardy, and M. R. Cookson. 2002. Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron 36: 1007–1019.
   PubMed Web of Science ®Google Scholar
• Pinon, L. G., G. Middleton, and A. M. Davies. 1997. Bcl-2 is required for cranial sensory neuron survival at defined stages of embryonic development. Development 124: 4173–4178.
   PubMedGoogle Scholar
• Rajagopalan, S., and J. K. Andersen. 2001. Alpha synuclein aggregation: is it the toxic gain of function responsible for neurodegeneration in Parkinson's disease? Mech. Ageing Dev. 122: 1499–1510.
   PubMedGoogle Scholar
• Rockenstein, E., L. A. Hansen, M. Mallory, Q. Trojanowski, D. Galasko, and E. Masliah. 2001. Altered expression of the synuclein family mRNA in Lewy body and Alzheimer's disease. Brain Res. 914: 48–56.
   PubMed Web of Science ®Google Scholar
• Saha, A. R., N. N. Ninkina, D. P. Hanger, B. H. Anderton, A. M. Davies, and V. L. Buchman. 2000. Induction of neuronal death by alpha-synuclein. Eur. J. Neurosci. 12: 3073–3077.
   PubMed Web of Science ®Google Scholar
• Schluter, O. M., F. Fornai, M. G. Alessandri, S. Takamori, M. Geppert, R. Jahn, and T. C. Sudhof. 2003. Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice. Neuroscience 118: 985–1002.
   PubMed Web of Science ®Google Scholar
• Serpell, L. C., J. Berriman, R. Jakes, M. Goedert, and R. A. Crowther. 2000. Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation. Proc. Natl. Acad. Sci. USA 97: 4897–4902.
   PubMed Web of Science ®Google Scholar
• Specht, C. G., and R. Schoepfer. 2001. Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci. 2: 11. [Online.] http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=11591219 .
   PubMed Web of Science ®Google Scholar
• Suzuki, K., E. Iseki, O. Katsuse, A. Yamaguchi, K. Katsuyama, I. Aoki, S. Yamanaka, and K. Kosaka. 2003. Neuronal accumulation of alpha- and beta-synucleins in the brain of a GM2 gangliosidosis mouse model. Neuroreport 14: 551–554.
   PubMedGoogle Scholar
• Tabrizi, S. J., M. Orth, J. M. Wilkinson, J. W. Taanman, T. T. Warner, J. M. Cooper, and A. H. Schapira. 2000. Expression of mutant alpha-synuclein causes increased susceptibility to dopamine toxicity. Hum. Mol. Genet. 9: 2683–2689.
   PubMed Web of Science ®Google Scholar
• Tanaka, Y., S. Engelender, S. Igarashi, R. K. Rao, T. Wanner, R. E. Tanzi, A. L. Sawa, V. Dawson, T. M. Dawson, and C. A. Ross. 2001. Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis. Hum. Mol. Genet. 10: 919–926.
   PubMed Web of Science ®Google Scholar
• Tiunova, A. A., K. V. Anokhin, A. R. Saha, O. Schmidt, D. P. Hanger, B. H. Anderton, A. M. Davies, N. N. Ninkina, and V. L. Buchman. 2000. Chicken synucleins: cloning and expression in the developing embryo. Mech. Dev. 99: 195–198.
   PubMedGoogle Scholar
• Trojanowski, J. Q., and V. M. Lee. 2002. Parkinson's disease and related synucleinopathies are a new class of nervous system amyloidoses. Neurotoxicology 23: 457–460.
   PubMed Web of Science ®Google Scholar
• Tybulewicz, V. L., C. E. Crawford, P. K. Jackson, R. T. Bronson, and R. C. Mulligan. 1991. Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell 65: 1153–1163.
   PubMed Web of Science ®Google Scholar
• Uversky, V. N., J. Li, P. Souillac, I. S. Millett, S. Doniach, R. Jakes, M. Goedert, and A. L. Fink. 2002. Biophysical properties of the synucleins and their propensities to fibrillate. Inhibition of alpha-synuclein assembly by beta- and gamma-synucleins. J. Biol. Chem. 277: 11970–11978.
   PubMed Web of Science ®Google Scholar
• van der Putten, H., K. H. Wiederhold, A. Probst, S. Barbieri, C. Mistl, S. Danner, S. Kauffmann, K. Hofele, W. P. Spooren, M. A. Ruegg, S. Lin, P. Caroni, B. Sommer, M. Tolnay, and G. Bilbe. 2000. Neuropathology in mice expressing human alpha-synuclein. J. Neurosci. 20: 6021–6029.
   PubMed Web of Science ®Google Scholar
• Wallace, V. C., D. F. Cottrell, P. J. Brophy, and S. M. Fleetwood-Walker. 2003. Focal lysolecithin-induced demyelination of peripheral afferents results in neuropathic pain behavior that is attenuated by cannabinoids. J. Neurosci. 23: 3221–3233.
   PubMed Web of Science ®Google Scholar
• Woolf, C., and S. Thompson. 1991. The induction and maintenance of central sensitization is dependent on N-methyl-d-aspartic acid receptor activation-implications for the treatment of postinjury pain hypersensitivity states. Pain 44: 293–299.
   PubMed Web of Science ®Google Scholar