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Mouse

Transgenic Mouse Models of α-synuclein-linked PD

α-Synuclein transgene	Promoter	Expression	Phenotype	Availability	Reference
Human WT	Human PDGF-β;	Throughout the brain	Pathology: 50% decrease in dopaminergic terminals at 12 months; inclusions in neocortex, hippocampus, olfactory bulb and, occasionally, substantia nigra Motor: Decrease in rotarod performance at 12 months		Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, Sagara Y, Sisk A, Mucke L. (2000). Dopaminergic loss and inclusion body formation in a-synuclein mice: implications for neurodegenerative disorders. Science, 287 (5456): 1265-9. [abstract]
Human Ala53Thr	Mouse Thy1	Spinal cord and most regions of the brain except the substantia nigra	Pathology: Axonal degeneration in spinal roots; denervation of neuromuscular junctions; inclusions and reactive gliosis in spinal cord and brainstem Motor: Decrease in rotarod performance at >40 days		van der Putten H, Wiederhold KH, Probst A, Barbieri S, Mistl C, Danner S, Kauffmann S, Hofele K, Spooren WP, Ruegg MA, Lin S, Caroni P, Sommer B, Tolnay M, Bilbe G (2000). Neuropathology in mice expressing human a-synuclein. Journal of Neuroscience, 20: 6021-6029. [abstract]
Human Ala30Pro	Mouse Thy1	Spinal cord and most regions of the brain except the substantia nigra	Pathology: Accumulation of α-synuclein in cortex, hippocampus, cerebellum, substantia nigra and striatum; no loss of TH-positive neurons or striatal dopamine; no increased sensitivity to MPTP Motor: No overt motor symptoms	Contact: Philipp Kahle at Ludwig Maximillians University, Munich, Germany	Kahle PJ, Neumann M, Ozmen L, Muller V, Jacobsen H, Schindzielorz A, Okochi M, Leimer U, van Der Putten H, Probst A, Kremmer E, Kretzschmar HA, Haass C. (2000). Subcellular localization of wild-type and Parkinson's disease-associated mutant a-synuclein in human and transgenic mouse brain. J. Neuroscience, 20: 6365-6373 [abstract]
Human Ala30Pro	4.5-kb rat TH	Catecholaminergic cell groups	Pathology: No loss of Th-positive neurons or striatal dopamine; no increased sensitivity to MPTP Motor: No change in rotarod performance		Rathke-Hartlieb S, Kahle PJ, Neumann M, Ozmen L, Haid S, Okochi M, Haass C, Schulz JB (2001). Sensitivity to MPTP is not increased in Parkinson's disease-associated mutant a-synuclein transgenic mice. J Neurochemistry, 77: 1181-1184 [abstract]
Human Ala53Thr or Ala30Pro	4.8-kb rat TH	Catecholaminergic cell groups	Pathology: No loss of TH-positive neurons or striatal dopamine; no inclusions despite accumulation of a-synuclein in nigral neurons Motor: No overt motor symptoms		Matsuoka Y, Vila M, Lincoln S, McCormack A, Picciano M, LaFrancois J, Yu X, Dickson D, Langston WJ, McGowan E, Farrer M, Hardy J, Duff K, Przedborski S, Di Monte DA (2001). Lack of nigral pathology in transgenic mice expressing human a-synuclein driven by the tyrosine hydroxylase promoter. Neurobiology of Disease, 8: 535-539. [abstract]
WT or doubly mutated (Ala53Thr and Ala30Pro)	9-kb rat TH	Catecholaminergic cell groups	Pathology: Decrease in striatal dopamine at >16 months; beaded nigral axons; changes seen in doubly mutated but not WT mice Motor: Decrease in amphetamine-induced locomotion in young mice; decrease in locomotor activity and coordination at 13 months in doubly mutated but not WT mice		Richfield EK, Thiruchelvam MJ, Cory-Slechta DA, Wuertzer C, Gainetdinov RR, Caron MG, Di Monte DA, Federoff HJ (2002). Behavioral and neurochemical effects of wild-type and mutated human a-synuclein in transgenic mice. Exp. Neurol., (175: 35-48. [abstract]
WT or Ala53Thr	Mouse PrP	Throughout the brain and spinal cord	Pathology: Inclusions in spinal horn, brainstem and deep cerebellar nuclei; dystrophic neurites in spinal cord and caudate/putament at >8 months; axonal degeneration in spinal roots at >12 months; all changes seen in Ala53Thr but not WT mice Motor: Decreased ambulation, weight loss, neglect of grooming, hindlimb paralysis, loss of righting reflex, inability to stand or feed and, eventually, death; all changes seen in Ala53Thr but not WT mice	The Jackson Laboratory Data Sheet	Giasson BI, Duda JE, Quinn SM, Zhang B, Trojanowski JQ, Lee VM (2002). Neuronal a-synucleinopathy with severe movement disorder in mice expressing A53T human a-synuclein. Neuron, 34: 521-533. [abstract]
WT or Ala53Thr or Ala30Pro	Mouse PrP	Throughout the brainstem and spinal cord	Pathology: Accumulation of insoluble a-synuclein aggregates and reactive gliosis in the dorsal midbrain, brainstem an deep cerebellar nuclei; changes seen in Ala53Thr but not Ala30Pro or WT mice Motor: Progressive motor dysfunction at >10-15 months, followed by death in Ala53Thr but not Ala30Pro or WT mice		Lee MK, Stirling W, Xu Y, Xu X, Qui D, Mandir AS, Dawson TM, Copeland NG, Jenkins NA, Price DL (2002). Human a-synuclein harboring familial Parkinson's disease-linked Ala-53 à Thr mutation causes neurodegenerative disease with a-synuclein aggregation in transgenic mice. Proc Natl Acad. Sci., 99: 8968-8973. [abstract]

Last updated February 09, 2005