Updated 14 April 2005

General Information

Transgene: human α-synuclein (α-syn) cDNA

Mutation: A30P

Promoter: neuron specific Thy-1

Mouse Strain: C57BL/6

Phenotype

Neuropathological Analysis:

Strong expression of transgenic (Tg) human [A30P]α-syn mRNA and protein in Northern and Western blot analysis of whole brain. In the two highest expressing lines (18, 31), expression was approximately twice that of endogenous mouse wt α-syn. (in Kahle 2001, Tg expression was up to three times that of endogenous α-syn expression.)

Expression of 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).

The mutant 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.

Behavioral analysis:

No overt motor abnormalities to 1 year of age.

Availability

Patents:

References

Primary:

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 α-synuclein in human transgenic mouse brain. J Neurosci. 2000 Sep 1;20(17):6365-73. Abstract .

Associated:

Frasier M, Walzer M, McCarthy L, Magnuson D, Lee JM, Haas C, Kahle P, Wolozin B. Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein. Exp Neurol. 192(2):274-87, 2005. Abstract.

Neumann M, Kahle PJ, Giasson BI, Ozmen L, Borroni E, Spooren W, Muller V, Odoy S, Fujiwara H, Hasegawa M, Iwatsubo T, Trojanowski JQ, Kretzschmar HA, Haass C. Misfolded proteinase K-resistant hyperphosphorylated α-synuclein in aged transgenic mice with locomotor deterioration and in human α-synucleinopathies. J Clin Invest 2002 Nov;110(10):1429-39. Abstract.

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 α-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse model. Am J Pathol. 2001 Dec;159(6):2215-25. Abstract .