|Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥5,200,000 (Direct Cost: ¥5,200,000)
A positional cloning approach is taken for the study of tremor (TM) and zitter (ZI) mutant genes, causative genes for epilepsy with spongiform encephalopathy in spontaneously epileptic rat (SER, a homozygote for zitter (ZI) and tremor (TM) mutant genes). Genetic linkage analysys revealed that the TM and ZI genes were tightly linked to the synaptobrevin-2 (SYB2) gene, coding an integral membrane protein in synaptic vesicles, on chromosome 10, and the prion protein (PRNP) gene, coding a key membrane molecule of prion diseases, on chromosome 3, respectively, making them candidates for the mutant genes. The genomic DNA sequence of the SYB2 gene of the TRM rat strain (homozygote for the TM) and the exon 2 of the PRNP gene of the ZI rat strain (homozygote for the ZI) were identical to those of a control strain WTC.In addition, no difference was detected for expression of the SYB2 and the PRNP genes on the Northern blot analyzes of TRM, ZI and WTC brain, suggesting that the SYB2 and PRNP genes are not the TM and the ZI, respectively. Despite this finding, we would like to retain the two genes as candidates, since the biological functions of the SYB2 and PRNP genes are not yet perfectly understood. The assignments of the TM and ZI genes to rat chromosome 10q24 and 3q35 will be the first step towards the cloning of the TM and ZI genes.