Transgene: human wild-type α-synuclein (α-syn) cDNA
Promoter: neuron specific Thy-1
Mouse Strain: C57BL/6
Neuropathological Analysis:
Expression of transgenic (Tg) α-syn largely paralleled that of endogenous mouse α-syn, with the exception of the first postnatal week, when small but significant amounts of endogenous, but no Tg α-syn, was seen (as expected for Thy1 cassette). Tg expression was up to three times that of endogenous α-syn expression.
The wt human α-syn was found in neuronal cell bodies and was also anterogradely transported to synapses, in contrast to the endogenous mouse α-syn, which was not observed in the somal compartment. Abnormal Tg α-syn-positive neurites, a characteristic of Lewy body disease, were seen, occasionally emanating from neuronal cell body.
Tg α-syn, but not endogenous α-syn (or nonamyloidogenic β-syn), was found in detergent-insoluble fractions of fresh tissue.
Patents:
Primary:
Kahle PJ, Neumann M, Ozmen L, Muller V, Odoy S, Okamoto M, Jacobsen H, Iwatsubo T, Trojanowski JQ, Takaashi H, Wakabayashi K, Bogdanovic N, Riederer P, Kretzschmar HA, Haass C. Selective insolubility of "-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse model. Am J Pathol. 2001 Dec;159(6):2215-25. Abstract.
Secondary:
Kahle PJ, Neumann M, Ozmen L, Muller V, Jacobsen H, Schindzielorz A, Masayasu O, Leimer U, van der Putten H, Probst A, Kremmer E, Kretzschmar HA, Haass C. Subcellular localization for wild-type and Parkinson's disease-associated mutant "-synuclein in human transgenic mouse brain. J Neurosci. 2000 Sep 1;20(17):6365-73. Abstract
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