Updated 14 April 2005
Transgene: human α-synuclein (α-syn) cDNA
Promoter: neuron specific Thy-1
Mouse Strain: C57BL/6
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 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
Tg α-syn, but not endogenous α-syn (or nonamyloidogenic β-syn), was
found in detergent-insoluble fractions of fresh tissue.
No overt motor abnormalities to 1 year of age.
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.
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.
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
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.