Overview of Mouse Models of Parkinson's Disease

Wojciech Bobela1, Lu Zheng1, Bernard L. Schneider2

1 These authors contributed equally to this work, 2 Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne
Publication Name:  Current Protocols in Mouse Biology
Unit Number:   
DOI:  10.1002/9780470942390.mo140092
Online Posting Date:  September, 2014
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Parkinson's disease is a neurodegenerative disorder characterized by the loss of neurons in specific regions of the nervous system, notably in the substantia nigra pars compacta and, in most cases, by the deposition of intraneuronal inclusions named Lewy bodies. These pathological alterations have profound effects on the brain function, leading to the progressive development of various symptoms, the most prominent being the impaired initiation of voluntary movements caused by the loss of dopamine signaling in the basal ganglia. Here, we provide an overview of the mouse models of Parkinson's disease, with the goal of guiding selection of the most appropriate model for studying the question at hand. Pharmacological approaches targeting dopamine signaling and toxins leading to selective degeneration of nigral neurons are used to validate symptomatic treatments that aim at restoring effective dopaminergic function for motor control. Alternative mouse models are based on genetic modifications that are meant to reproduce the inherited alterations associated with familial forms of Parkinson's disease. Although genetic models have most often failed to induce overt degeneration of nigral dopaminergic neurons, they provide essential tools to explore the multifactorial etiology of this complex neurodegenerative disorder. Curr. Protoc. Mouse Biol. 4:121‐139 © 2014 by John Wiley & Sons, Inc.

Keywords: Parkinson's disease; mouse models of neurodegeneration; genetic factors; toxins

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Table of Contents

  • Introduction
  • Pharmaceutical Approaches to Model Parkinson's Disease
  • Assessing Deficits in Mouse Models of Parkinson's Disease
  • Conflict of Interest
  • Literature Cited
  • Tables
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Literature Cited

Literature Cited
  Anderson, G., Noorian, A.R., Taylor, G., Anitha, M., Bernhard, D., Srinivasan, S., and Greene, J.G. 2007. Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease. Exp. Neurol. 207:4‐12.
  Andres‐Mateos, E., Mejias, R., Sasaki, M., Li, X., Lin, B.M., Biskup, S., Zhang, L., Banerjee, R., Thomas, B., Yang, L., Liu, G., Beal, M.F., Huso, D.L., Dawson, T.M., and Dawson, V.L. 2009. Unexpected lack of hypersensitivity in LRRK2 knock‐out mice to MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine). J. Neurosci. 29:15846‐15850.
  Bendor, J.T., Logan, T.P., and Edwards, R.H. 2013. The function of α‐synuclein. Neuron 79:1044‐1066.
  Betarbet, R., Canet‐Aviles, R.M., Sherer, T.B., Mastroberardino, P.G., McLendon, C., Kim, J.H., Lund, S., Na, H.M., Taylor, G., Bence, N.F., Kopito, R., Seo, B.B., Yagi, T., Yagi, A., Klinefelter, G., Cookson, M.R., and Greenamyre, J.T. 2006. Intersecting pathways to neurodegeneration in Parkinson's disease: Effects of the pesticide rotenone on DJ‐1, α‐synuclein, and the ubiquitin‐proteasome system. Neurobiol. Dis. 22:404‐420.
  Bove, J., Zhou, C., Jackson‐Lewis, V., Taylor, J., Chu, Y., Rideout, H.J., Wu, D.C., Kordower, J.H., Petrucelli, L., and Przedborski, S. 2006. Proteasome inhibition and Parkinson's disease modeling. Ann. Neurol. 60:260‐264.
  Braak, H., Del Tredici, K., Rub, U., de Vos, R.A., Jansen Steur, E.N., and Braak, E. 2003. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol. Aging 24:197‐211.
  Burre, J., Sharma, M., Tsetsenis, T., Buchman, V., Etherton, M.R., and Sudhof, T.C. 2010. α‐Synuclein promotes SNARE‐complex assembly in vivo and in vitro. Science 329:1663‐1667.
  Cannon, J.R., Tapias, V., Na, H.M., Honick, A.S., Drolet, R.E., and Greenamyre, J.T. 2009. A highly reproducible rotenone model of Parkinson's disease. Neurobiol. Dis. 34:279‐290.
  Chandra, S., Gallardo, G., Fernandez‐Chacon, R., Schluter, O.M., and Sudhof, T.C. 2005. α‐Synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 123:383‐396.
  Chen, Y. and Dorn, G.W. II. 2013. PINK1‐phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 340:471‐475.
  Chesselet, M.F., Richter, F., Zhu, C., Magen, I., Watson, M.B., and Subramaniam, S.R. 2012. A progressive mouse model of Parkinson's disease: The Thy1‐aSyn (“Line 61”) mice. Neurotherapeutics 9:297‐314.
  Clark, I.E., Dodson, M.W., Jiang, C., Cao, J.H., Huh, J.R., Seol, J.H., Yoo, S.J., Hay, B.A., and Guo, M. 2006. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441:1162‐1166.
  Dauer, W., Kholodilov, N., Vila, M., Trillat, A.C., Goodchild, R., Larsen, K.E., Staal, R., Tieu, K., Schmitz, Y., Yuan, C.A., Rocha, M., Jackson‐Lewis, V., Hersch, S., Sulzer, D., Przedborski, S., Burke, R., and Hen, R. 2002. Resistance of α‐synuclein null mice to the parkinsonian neurotoxin MPTP. Proc. Natl. Acad. Sci. U.S.A. 99:14524‐14529.
  Dawson, T.M., Ko, H.S., and Dawson, V.L. 2010. Genetic animal models of Parkinson's disease. Neuron 66:646‐661.
  Dowd, E., Monville, C., Torres, E.M., and Dunnett, S.B. 2005. The Corridor Task: A simple test of lateralised response selection sensitive to unilateral dopamine deafferentation and graft‐derived dopamine replacement in the striatum. Brain Res. Bull. 68:24‐30.
  Drolet, R.E., Cannon, J.R., Montero, L., and Greenamyre, J.T. 2009. Chronic rotenone exposure reproduces Parkinson's disease gastrointestinal neuropathology. Neurobiol. Dis. 36:96‐102.
  Ekstrand, M.I. and Galter, D. 2009. The MitoPark Mouse ‐ an animal model of Parkinson's disease with impaired respiratory chain function in dopamine neurons. Parkinsonism Relat. Disord. 15:S185‐S188.
  Ekstrand, M.I., Terzioglu, M., Galter, D., Zhu, S., Hofstetter, C., Lindqvist, E., Thams, S., Bergstrand, A., Hansson, F.S., Trifunovic, A., Hoffer, B., Cullheim, S., Mohammed, A.H., Olson, L., and Larsson, N.G. 2007. Progressive parkinsonism in mice with respiratory‐chain‐deficient dopamine neurons. Proc. Natl. Acad. Sci. U.S.A. 104:1325‐1330.
  Fornai, F., Schluter, O.M., Lenzi, P., Gesi, M., Ruffoli, R., Ferrucci, M., Lazzeri, G., Busceti, C.L., Pontarelli, F., Battaglia, G., Pellegrini, A., Nicoletti, F., Ruggieri, S., Paparelli, A., and Sudhof, T.C. 2005. Parkinson‐like syndrome induced by continuous MPTP infusion: Convergent roles of the ubiquitin‐proteasome system and α‐synuclein. Proc. Natl. Acad. Sci. U.S.A. 102:3413‐3418.
  Garcia‐Reitbock, P., Anichtchik, O., Bellucci, A., Iovino, M., Ballini, C., Fineberg, E., Ghetti, B., Della Corte, L., Spano, P., Tofaris, G.K., Goedert, M., and Spillantini, M.G. 2010. SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease. Brain 133:2032‐2044.
  Giasson, B.I., Duda, J.E., Quinn, S.M., Zhang, B., Trojanowski, J.Q., and Lee, V.M. 2002. Neuronal α‐synucleinopathy with severe movement disorder in mice expressing A53T human α‐synuclein. Neuron 34:521‐533.
  Goldberg, M.S., Fleming, S.M., Palacino, J.J., Cepeda, C., Lam, H.A., Bhatnagar, A., Meloni, E.G., Wu, N., Ackerson, L.C., Klapstein, G.J., Gajendiran, M., Roth, B.L., Chesselet, M.F., Maidment, N.T., Levine, M.S., and Shen, J. 2003. Parkin‐deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J. Biol. Chem. 278:43628‐43635.
  Goldberg, M.S., Pisani, A., Haburcak, M., Vortherms, T.A., Kitada, T., Costa, C., Tong, Y., Martella, G., Tscherter, A., Martins, A., Bernardi, G., Roth, B.L., Pothos, E.N., Calabresi, P., and Shen, J. 2005. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism‐linked gene DJ‐1. Neuron 45:489‐496.
  Grealish, S., Mattsson, B., Draxler, P., and Bjorklund, A. 2010. Characterisation of behavioural and neurodegenerative changes induced by intranigral 6‐hydroxydopamine lesions in a mouse model of Parkinson's disease. Eur. J. Neurosci. 31:2266‐2278.
  Greten‐Harrison, B., Polydoro, M., Morimoto‐Tomita, M., Diao, L., Williams, A.M., Nie, E.H., Makani, S., Tian, N., Castillo, P.E., Buchman, V.L., and Chandra, S.S. 2010. αβγ‐Synuclein triple knockout mice reveal age‐dependent neuronal dysfunction. Proc. Natl. Acad. Sci. U.S.A. 107:19573‐19578.
  Hazell, A.S., Itzhak, Y., Liu, H., and Norenberg, M.D. 1997. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) decreases glutamate uptake in cultured astrocytes. J. Neurochem. 68:2216‐2219.
  Heikkila, R.E., Hess, A., and Duvoisin, R.C. 1984. Dopaminergic neurotoxicity of 1‐methyl‐4‐phenyl‐1,2,5,6‐tetrahydropyridine in mice. Science 224:1451‐1453.
  Hinzen, D., Hornykiewicz, O., Kobinger, W., Pichler, L., Pifl, C., and Schingnitz, G. 1986. The dopamine autoreceptor agonist B‐HT 920 stimulates denervated postsynaptic brain dopamine receptors in rodent and primate models of Parkinson's disease: a novel approach to treatment. Eur. J. Pharmacol. 131:75‐86.
  Hoglinger, G.U., Feger, J., Prigent, A., Michel, P.P., Parain, K., Champy, P., Ruberg, M., Oertel, W.H., and Hirsch, E.C. 2003. Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J. Neurochem. 84:491‐502.
  Hoglinger, G.U., Oertel, W.H., and Hirsch, E.C. 2006. The rotenone model of parkinsonism—the five years inspection. J. Neural Transm. Suppl. 70:269‐272.
  Inden, M., Kitamura, Y., Abe, M., Tamaki, A., Takata, K., and Taniguchi, T. 2011. Parkinsonian rotenone mouse model: Reevaluation of long‐term administration of rotenone in C57BL/6 mice. Biol. Pharm. Bull. 34:92‐96.
  Itier, J.M., Ibanez, P., Mena, M.A., Abbas, N., Cohen‐Salmon, C., Bohme, G.A., Laville, M., Pratt, J., Corti, O., Pradier, L., Ret, G., Joubert, C., Periquet, M., Araujo, F., Negroni, J., Casarejos, M.J., Canals, S., Solano, R., Serrano, A., Gallego, E., Sanchez, M., Denefle, P., Benavides, J., Tremp, G., Rooney, T.A., Brice, A., and Garcia de Yebenes, J. 2003. Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum. Mol. Genet. 12:2277‐2291.
  Janezic, S., Threlfell, S., Dodson, P.D., Dowie, M.J., Taylor, T.N., Potgieter, D., Parkkinen, L., Senior, S.L., Anwar, S., Ryan, B., Deltheil, T., Kosillo, P., Cioroch, M., Wagner, K., Ansorge, O., Bannerman, D.M., Bolam, J.P., Magill, P.J., Cragg, S.J., and Wade‐Martins, R. 2013. Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model. Proc. Natl. Acad. Sci. U.S.A. 110:E4016‐E4025.
  Jeon, B.S., Jackson‐Lewis, V., and Burke, R.E. 1995. 6‐Hydroxydopamine lesion of the rat substantia nigra: Time course and morphology of cell death. Neurodegeneration 4:131‐137.
  Kitada, T., Pisani, A., Porter, D.R., Yamaguchi, H., Tscherter, A., Martella, G., Bonsi, P., Zhang, C., Pothos, E.N., and Shen, J. 2007. Impaired dopamine release and synaptic plasticity in the striatum of PINK1‐deficient mice. Proc. Natl. Acad. Sci. U.S.A. 104:11441‐11446.
  Kitada, T., Tong, Y., Gautier, C.A., and Shen, J. 2009. Absence of nigral degeneration in aged parkin/DJ‐1/PINK1 triple knockout mice. J. Neurochem. 111:696‐702.
  Kondapalli, C., Kazlauskaite, A., Zhang, N., Woodroof, H.I., Campbell, D.G., Gourlay, R., Burchell, L., Walden, H., Macartney, T.J., Deak, M., Knebel, A., Alessi, D.R., and Muqit, M.M. 2012. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol. 2:120080.
  Kupsch, A., Gerlach, M., Pupeter, S.C., Sautter, J., Dirr, A., Arnold, G., Opitz, W., Przuntek, H., Riederer, P., and Oertel, W.H. 1995. Pretreatment with nimodipine prevents MPTP‐induced neurotoxicity at the nigral, but not at the striatal level in mice. Neuroreport 6:621‐625.
  Langston, J.W., Ballard, P., Tetrud, J.W., and Irwin, I. 1983. Chronic Parkinsonism in humans due to a product of meperidine‐analog synthesis. Science 219:979‐980.
  Lauwers, E., Debyser, Z., Van Dorpe, J., De Strooper, B., Nuttin, B., and Baekelandt, V. 2003. Neuropathology and neurodegeneration in rodent brain induced by lentiviral vector‐mediated overexpression of α‐synuclein. Brain Pathol. 13:364‐372.
  Lee, B.D., Shin, J.H., VanKampen, J., Petrucelli, L., West, A.B., Ko, H.S., Lee, Y.I., Maguire‐Zeiss, K.A., Bowers, W.J., Federoff, H.J., Dawson, V.L., and Dawson, T.M. 2010. Inhibitors of leucine‐rich repeat kinase‐2 protect against models of Parkinson's disease. Nat. Med. 16:998‐1000.
  Li, X., Patel, J.C., Wang, J., Avshalumov, M.V., Nicholson, C., Buxbaum, J.D., Elder, G.A., Rice, M.E., and Yue, Z. 2010. Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson's disease mutation G2019S. J. Neurosci. 30:1788‐1797.
  Li, Y., Liu, W., Oo, T.F., Wang, L., Tang, Y., Jackson‐Lewis, V., Zhou, C., Geghman, K., Bogdanov, M., Przedborski, S., Beal, M.F., Burke, R.E., and Li, C. 2009. Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat. Neurosci. 12:826‐828.
  Luk, K.C., Kehm, V., Carroll, J., Zhang, B., O'Brien, P., Trojanowski, J.Q., and Lee, V.M. 2012. Pathological α‐synuclein transmission initiates Parkinson‐like neurodegeneration in nontransgenic mice. Science 338:949‐953.
  Lundblad, M., Picconi, B., Lindgren, H., and Cenci, M.A. 2004. A model of L‐DOPA‐induced dyskinesia in 6‐hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function. Neurobiol. Dis. 16:110‐123.
  Manning‐Bog, A.B., McCormack, A.L., Li, J., Uversky, V.N., Fink, A.L., and Di Monte, D.A. 2002. The herbicide paraquat causes up‐regulation and aggregation of α‐synuclein in mice: Paraquat and α‐synuclein. J. Biol. Chem. 277:1641‐1644.
  Manning‐Bog, A.B., Reaney, S.H., Chou, V.P., Johnston, L.C., McCormack, A.L., Johnston, J., Langston, J.W., and Di Monte, D.A. 2006. Lack of nigrostriatal pathology in a rat model of proteasome inhibition. Ann Neurol 60:256‐260.
  Masliah, E., Rockenstein, E., Veinbergs, I., Mallory, M., Hashimoto, M., Takeda, A., Sagara, Y., Sisk, A., and Mucke, L. 2000. Dopaminergic loss and inclusion body formation in α‐synuclein mice: Implications for neurodegenerative disorders. Science 287:1265‐1269.
  Matsuoka, Y., Vila, M., Lincoln, S., McCormack, A., Picciano, M., LaFrancois, J., Yu, X., Dickson, D., Langston, W.J., McGowan, E., Farrer, M., Hardy, J., Duff, K., Przedborski, S., and Di Monte, D.A. 2001. Lack of nigral pathology in transgenic mice expressing human α‐synuclein driven by the tyrosine hydroxylase promoter. Neurobiol. Dis. 8:535‐539.
  McCormack, A.L. and Di Monte, D.A. 2003. Effects of L‐dopa and other amino acids against paraquat‐induced nigrostriatal degeneration. J. Neurochem. 85:82‐86.
  McNaught, K.S., Perl, D.P., Brownell, A.L., and Olanow, C.W. 2004. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. Ann. Neurol. 56:149‐162.
  Narendra, D., Tanaka, A., Suen, D.F., and Youle, R.J. 2008. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol. 183:795‐803.
  Park, J., Lee, S.B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., Kim, J.‐M., and Chung, J. 2006. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441:1157‐1161.
  Przedborski, S. and Vila, M. 2003. The 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mouse model: A tool to explore the pathogenesis of Parkinson's disease. Ann. N.Y. Acad. Sci. 991:189‐198.
  Ramonet, D., Daher, J.P., Lin, B.M., Stafa, K., Kim, J., Banerjee, R., Westerlund, M., Pletnikova, O., Glauser, L., Yang, L., Liu, Y., Swing, D.A., Beal, M.F., Troncoso, J.C., McCaffery, J.M., Jenkins, N.A., Copeland, N.G., Galter, D., Thomas, B., Lee, M.K., Dawson, T.M., Dawson, V.L., and Moore, D.J. 2011. Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2. PLoS One 6:e18568.
  Rappold, P.M., Cui, M., Chesser, A.S., Tibbett, J., Grima, J.C., Duan, L., Sen, N., Javitch, J.A., and Tieu, K. 2011. Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation transporter‐3. Proc. Natl. Acad. Sci. U.S.A. 108:20766‐20771.
  Sanberg, P.R. 1980. Haloperidol‐induced catalepsy is mediated by postsynaptic dopamine receptors. Nature 284:472‐473.
  Schwarting, R.K., Sedelis, M., Hofele, K., Auburger, G.W., and Huston, J.P. 1999. Strain‐dependent recovery of open‐field behavior and striatal dopamine deficiency in the mouse MPTP model of Parkinson's disease. Neurotox. Res. 1:41‐56.
  Shook, B.C., Rassnick, S., Osborne, M.C., Davis, S., Westover, L., Boulet, J., Hall, D., Rupert, K.C., Heintzelman, G.R., Hansen, K., Chakravarty, D., Bullington, J.L., Russell, R., Branum, S., Wells, K.M., Damon, S., Youells, S., Li, X., Beauchamp, D.A., Palmer, D., Reyes, M., Demarest, K., Tang, Y., Rhodes, K., and Jackson, P.F. 2010. In vivo characterization of a dual adenosine A2A/A1 receptor antagonist in animal models of Parkinson's disease. J. Med. Chem. 53:8104‐8115.
  Skalisz, L.L., Beijamini, V., Joca, S.L., Vital, M.A., Da Cunha, C., and Andreatini, R. 2002. Evaluation of the face validity of reserpine administration as an animal model of depression—Parkinson's disease association. Prog. Neuropsychopharmacol. Biol. Psychiatry 26:879‐883.
  Spillantini, M.G., Schmidt, M.L., Lee, V.M., Trojanowski, J.Q., Jakes, R., and Goedert, M. 1997. α‐Synuclein in Lewy bodies. Nature 388:839‐840.
  St Martin, J.L., Klucken, J., Outeiro, T.F., Nguyen, P., Keller‐McGandy, C., Cantuti‐Castelvetri, I., Grammatopoulos, T.N., Standaert, D.G., Hyman, B.T., and McLean, P.J. 2007. Dopaminergic neuron loss and up‐regulation of chaperone protein mRNA induced by targeted over‐expression of α‐synuclein in mouse substantia nigra. J. Neurochem. 100:1449‐1457.
  Stott, S.R. and Barker, R.A. 2014. Time course of dopamine neuron loss and glial response in the 6‐OHDA striatal mouse model of Parkinson's disease. Eur. J. Neurosci. 39:1042‐1056.
  Tasselli, M., Chaumette, T., Paillusson, S., Monnet, Y., Lafoux, A., Huchet‐Cadiou, C., Aubert, P., Hunot, S., Derkinderen, P., and Neunlist, M. 2013. Effects of oral administration of rotenone on gastrointestinal functions in mice. Neurogastroenterol. Motil. 25:e183‐e193.
  Tofaris, G.K., Garcia Reitbock, P., Humby, T., Lambourne, S.L., O'Connell, M., Ghetti, B., Gossage, H., Emson, P.C., Wilkinson, L.S., Goedert, M., and Spillantini, M.G. 2006. Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human α‐synuclein(1‐120): implications for Lewy body disorders. J. Neurosci. 26:3942‐3950.
  Tong, Y., Pisani, A., Martella, G., Karouani, M., Yamaguchi, H., Pothos, E.N., and Shen, J. 2009. R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice. Proc. Natl. Acad. Sci. U.S.A. 106:14622‐14627.
  Tong, Y., Yamaguchi, H., Giaime, E., Boyle, S., Kopan, R., Kelleher, R.J., III, and Shen, J. 2010. Loss of leucine‐rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of α‐synuclein, and apoptotic cell death in aged mice. Proc. Natl. Acad. Sci. U.S.A. 107:9879‐9884.
  Ungerstedt, U. 1968. 6‐Hydroxy‐dopamine induced degeneration of central monoamine neurons. Eur. J. Pharmacol. 5:107‐110.
  Van der Putten, H., Wiederhold, K.H., Probst, A., Barbieri, S., Mistl, C., Danner, S., Kauffmann, S., Hofele, K., Spooren, W.P., Ruegg, M.A., Lin, S., Caroni, P., Sommer, B., Tolnay, M., and Bilbe, G. 2000. Neuropathology in mice expressing human α‐synuclein. J. Neurosci. 20:6021‐6029.
  Viyoch, J., Ohdo, S., Yukawa, E., and Higuchi, S. 2001. Dosing time‐dependent tolerance of catalepsy by repetitive administration of haloperidol in mice. J. Pharmacol. Exp. Ther. 298:964‐969.
  Von Coelln, R., Thomas, B., Savitt, J.M., Lim, K.L., Sasaki, M., Hess, E.J., Dawson, V.L., and Dawson, T.M. 2004. Loss of locus coeruleus neurons and reduced startle in parkin null mice. Proc. Natl. Acad. Sci. U.S.A. 101:10744‐10749.
  Wang, X., Winter, D., Ashrafi, G., Schlehe, J., Wong, Y.L., Selkoe, D., Rice, S., Steen, J., LaVoie, M.J., and Schwarze, T.L. 2011. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147:893‐906.
  Womer, D.E., Jones, B.C., and Erwin, V.G. 1994. Characterization of dopamine transporter and locomotor effects of cocaine, GBR 12909, epidepride, and SCH 23390 in C57BL and DBA mice. Pharmacol. Biochem. Behav. 48:327‐335.
  Xie, W., Li, X., Li, C., Zhu, W., Jankovic, J., and Le, W. 2010. Proteasome inhibition modeling nigral neuron degeneration in Parkinson's disease. J. Neurochem. 115:188‐199.
  Yang, Y., Gehrke, S., Imai, Y., Huang, Z., Ouyang, Y., Wang, J.‐W., Yang, L., Beal, M.F., Vogel, H., and Lu, B. 2006. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc. Natl. Acad. Sci. U.S.A. 103:10793‐10798.
  Yong‐Kee, C.J., Sidorova, E., Hanif, A., Perera, G., and Nash, J.E. 2012. Mitochondrial dysfunction precedes other sub‐cellular abnormalities in an in vitro model linked with cell death in Parkinson's disease. Neurotox. Res. 21:185‐194.
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