| General Note | This line was originally designated G2-3. Lines H5 and N2-5 were also generated. Mice transgenic for lines H5 and N2-5 display a phenotype similar to that displayed by mice carrying line 23. A fourth line of transgenic mice (L5) which did not develop disease, expressed a low level of the mutant human protein. Transgenic mice express high levels of mutant human Ala53Thr alpha synuclein in brain and develop an adult onset neurodegenerative disease characterized by progressive motoric dysfunction that rapidly progresses to death in most animals. Expression of the mutant protein is associated with significantly enhanced in vivo neurotoxicity. Transgenic mice develop motor signs characterized by sustained posturing, reduced amplitude, and abundance of spontaneous activity. In many instances, the affected mice seem to exhibit bradykinesia, mild ataxia, and dystonia. These mice eventually develop progressive loss of righting reflex and paralysis. Although the abundance of alpha-synuclein transcript in both human and mouse substantia nigra (SN) decreases with age, levels of alpha-synuclein protein remain at high levels, resulting in an elevated level of alpha-synuclein relative to other synucleins. The level of A53T mutant human alpha-synuclein (SNCA) protein in brains of mice of lines N2-5 and H5, adjusted for transgene copy number, becomes significantly elevated as the mice age in comparison with the brain levels of human alpha-synuclein in mice bearing similar transgenes encoding A30P mutant [Tg(Prnp-SNCA*A30P)2Dpr] and wild-type [Tg(Prnp-SNCA)22Dpr] human SNCA, which do not change with age. (The present A53T mutant line, G2-3, was not analyzed in these studies because the severity of its brain pathology might interfere with the results.) (J:137012) |
