|Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
We previously identified a novel parkin gene responsible for the pathogenesis of autosomal recessive juvenile parkinsonism (AR-JP). AR-JP is a distinct clinical and genetic entity with selective degeneration of the neurons in the substantia nigra. To gain some insight into the physiological role of the parkin gene, in this present study we assessed the expression of Parkin protein during the rat development by using immunoblot analysis. In the adult rat, the expression level of the protein was high in all regions of the central nervous system examined (cerebral cortex, hippocampus, striatum, hypothalamus, midbrain, cerebellum, medulla-pons, and spinal cord) and in the heart, but very low in other tissues (liver, lung, and kidney). At the early postnatal stage, Parkin protein was expressed at a lower level in all of the brain regions and gradually increased with postnatal growth and maturity. Parkin was also detected in the spinal cord and heart at this early stage, but its expression did not increase progressively in these locations during development. These results indicate that Parkin protein was not confined to substantia nigra, but also expressed in other brain regions. Parkin protein may play a physiological role in the brain, especially at later postnatal stages of brain development in the rat. We also determined the expression of the parkin gene during neuronal differentiation of rat PC-12 cells. The gene was expressed in differentiated PC-12 cells, but not in undifferentiated growing PC-12 cells. These results may indicate a significant role for the parkin gene in the neuronal differentiation and function.