The molecular cloning and expression of a human synaptic vesicle amine transporter that suppresses MPP+ toxicity.

A synaptic vesicle amine transporter cDNA, termed hSVAT, has been isolated by the reverse transcription and polymerase chain reaction (PCR) technique from human substantia nigra and subsequent screening of a human substantia nigra library. The hSVAT sequence obtained is highly homologous to the rat SVAT sequence (92% homology) and is essentially identical to the human sequence identified recently by Surratt and colleagues [33]. This labelled hSVAT cDNA detected a single band (approximately 5.0 kb) when used as a probe for Northern analysis of human nigral RNA extract. In situ hybridization studies using hSVAT specific antisense oligonucleotides showed a strong hybridization signal concentrated over the cells of the substantia nigra pars compacta. This cDNA sequence when expressed in chinese hamster ovary (CHO) cells conferred resistance to MPP+ the toxic metabolite of MPTP and cells containing it accumulated dopamine.