Mice hemizygous for the human synuclein (alpha-syn) transgene, (SNCA) are viable and fertile. Expression of the transgene is regulated by the tetracycline operator (tetO); also called tetracycline-responsive element (TRE, TetRE) or tet-operator). When mated to a strain expressing tetracycline-controlled transactivator protein (tTA), expression of the SNCA protein may be regulated with tetracycline or its analog doxycycline (dox) in the double mutant offspring. The formation of alpha-syn aggregates is a key step in the pathogenesis of Parkinson's disease. These aggregates cause formation of fibrillar aggregates causing various forms of cytotoxicity, including impairment of proteasomal and lysosomal activities, disruption of ER-Golgi traffic and microtubule-based transport, and dysfunction of mitochondria. SNCA mice develop age-dependent, progressive neurodegeneration. These mice may be useful for studying the Parkinson's disease pathogenesis and neurodegeneration elicited by the toxic effects of aggregation and somatic accumulation of SNCA.
For example, when bred to a strain expressing rtTA or tTA in forebrain neurons (see Stock No. 007004 for example), this mutant mouse strain may be useful in studies of neurodegeneration.
