Alpha-synuclein (α-syn) is a 140 amino acid, intrinsically disordered protein with a potential role in neurotransmitter vesicle release. The protein is natively unfolded under physiological conditions, and is expressed predominantly in neural tissue. α-syn is associated with neuropathological conditions in Parkinson’s disease, where the protein misfolds into oligomers and fibrils resulting in aggregates in Lewy bodies. Here we report the molecular cloning of SNCA cDNA encoding porcine α-syn and transcript variants hereof. Six transcripts coding for porcine α-syn are presented in the report, of which three result from exon skipping, generating in-frame splicing of coding exons 3 and 5. The splicing pattern of these alternative spliced variants is conserved between human and pig. All the observed in-frame deletions yield significantly shorter α-syn proteins compared with the 140 amino acid full-length protein. Expression analysis performed by real-time quantitative RT-PCR revealed a differential expression of the six transcript splicing variants in different pig organs and tissues. Common for all splicing variants, a very high transcript expression was detected in brain tissues and in spinal cord and very low or no expression outside the central nervous system. The porcine α-syn protein demonstrated markedly different biophysical characteristics compared with its human counterpart. No fibrillation of porcine α-syn was observed with the pig wild-type α-syn and A30P α-syn, and both variants show significantly reduced ability to bind to lipid vesicles. Overexpression of mutated porcine α-syn might recapitulate the human PD pathogenesis and lead to the identification of genetic modifiers of the disease.

α-突触核蛋白（α-syn）是一个140个氨基酸的内在无序蛋白，在神经递质囊泡释放中具有潜在作用。该蛋白质在生理条件下天然解折叠，并主要在神经组织中表达。α-syn与帕金森氏病的神经病理学状况有关，在该病中，蛋白质误折叠为寡聚体和原纤维，导致路易体中聚集。在这里我们报告SNCA的分子克隆编码猪α-syn及其转录本变体的cDNA。报告中提供了六个编码猪α-syn的转录本，其中三个转录本来自外显子跳跃，产生了编码外显子3和5的框内剪接。这些替代剪接变体的剪接模式在人与猪之间是保守的。与140个氨基酸的全长蛋白相比，所有观察到的框内缺失均产生明显短得多的α-syn蛋白。通过实时定量RT-PCR进行的表达分析揭示了六个转录本剪接变体在不同猪器官和组织中的差异表达。对于所有剪接变体常见，在脑组织和脊髓中检测到非常高的转录表达，而在中枢神经系统外检测到非常低或没有表达。与人的猪相比，猪的α-syn蛋白具有明显不同的生物物理特性。猪野生型α-syn和A30Pα-syn未观察到猪α-syn的原纤化，并且两个变体均显示出与脂质囊泡结合的能力显着降低。猪α-syn突变基因的过表达可能会重述人类PD的发病机理，并导致对该疾病的遗传修饰因子的鉴定。