DIFFERENTIAL EXPRESSION OF THE PARKIN GENE IN THE HUMAN BRAIN AND PERIPHERAL LEUKOCYTES

Molecular cloning of the responsible gene on chromosome 6q25.2-27 for autosomal recessive juvenile parkinsonism (AR-JP) identified a novel p rotein of unknown function, named parkin. In patients with AR-JP, dele tions most commonly involve exons 3-5 in the parkin gene. For mutation screening we tried to analyze the parkin transcript amplified by RT-P CR. Based on the assumption that illegitimate transcription of the par kin gene may occur in every cell type, we successfully amplified the p arkin message from human peripheral leukocytes using RT-PCR. The parki n transcript in leukocytes was smaller in size than the full-length tr anscript in the brain. DNA sequencing determined that exons 3-5 were s pliced out in the normal human leukocyte transcript. Our results demon strate that alternative splicing produces distinct parkin transcripts in different tissues. Moreover, physiological splicing of deletion-pro ne exons may provide an important clue to understanding the pathogenes is of AR-JP. (C) 1998 Elsevier Science Ireland Ltd. All rights reserve d.