Despite the absence of prominent changes in the SNc, tg α-Syn mice do develop robust cell death and neuronal loss in other regions of brain and in spinal cord [395]. These tg mice express high levels of human wild-type or mutant (A53T and A30P) α-Syn under the control of the mouse prion protein promoter [390]. Mice expressing A53T α-Syn (lines G2-3 and H5), but not mice expressing wild-type (line I2-2) or A30P (line O2) α-Syn, develop adult-onset progressive motor deficits, including reduced spontaneous activity with bradykinesia, mild ataxia and dystonia, at ~10–15 months of age followed by rapidly progressive paralysis and death [390]. A53T mice develop intraneuronal inclusions, mitochondrial degeneration, and cell death in neocortex, brainstem, and spinal cord [395]. Brainstem neurons and spinal motor neurons display a prominent chromatolysis reaction and axonal spheroids, typical of that seen after axonal injury [396]. A53T mice form LB-like inclusions in neocortical and spinal motor neurons and have progressive, profound loss (~75%) of motor neurons that causes their paralysis [341,395].