Snca^tm1(SNCA)Ge

A targeting vector consisting of loxP-flanked human alpha-synuclein, followed by human alpha-synuclein with three alanine to proline substitutions at residues 30, 56, and 76 (A30P, A56P, A76P), IRES, a placental alkaline phosphatase (pLAP) reporter gene, and FRT-flanked neomycin gene was targeted to exon 3, thereby disrupting the mouse gene and placing the wild-type human gene under the control of the endogenous mouse regulatory region. The neomycin selection cassette was removed via flp-mediated recombination. RT-PCR detected a 512 bp transcript corresponding to the wild-type human alpha-synuclein, as well as a 566 bp transcript indicating that the mutant human alpha-synuclein transcript is also expressed due to read-through transcription. However, expression of the human mutant protein is approximately 10-fold lower than in the derivative allele expressing only the mutant SNCA (Sncatm1.1(SNCA*)Ge). The triple alanine to proline substitutions favors oligomer formation. (J:314280)