Molecular characteristics of porcine alpha-synuclein splicing variants

Knud Larsen*, Rikke Bæk, Cagla Sahin, Lars Kjær, Gunna Christiansen, Janni Nielsen, Leila Farajzadeh, Daniel E Otzen

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


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.

Original languageEnglish
Pages (from-to)121-133
Number of pages13
Publication statusPublished - Jan 2021


  • Alpha-synuclein
  • Fibrillation
  • Methylation
  • Pig
  • SNCA


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