| Budget Amount *help |
¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1986: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1985: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1984: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Research Abstract |
A new human polyomavirus, JC virus, first isolated in Japan by us, has been shown to be highly neurooncogenic to hamsters, and was named JC virus Tokyo-1 strain (Abb: JCT). JCT has been shown to induce constantly mid-cerebellar neuroectodermal tumors in hamsters, which are very similar to human medulloblastoma. The host range of JCT was wide, and tumorgeniciy was very high, compared to those isolated from U.S.A. and West Germany. To investigate this unique properties of JCT, we cloned JCT-DNA, and examined the genomic characters of DNA.
1. Origin of medulloblastoma: We cloned the T region of JCT-DNA, and labeled the antisence mRNA of JCT-T region with radioisotope, and examined JCT mRNA in the hamster cerebellum after inoculation by in situ hybridization. The mRNA was first detected in the cells of the cerebellar molecular layer between the external granular layer and the internal granular layer, as well as cells in the internal granular layer. Thus, it could be said that the cells in the developing external granular layer were infected with JCT, migrated into the internal granular layer carrying the integrated JCT genome, then express the phenotypic transformation in the internal granular layer.
2. Difference of JCT in restriction enzyme cleavaged pattern: To compare the JCT to those from other countries, we cloned JCT DNA directly from the original PML brain as well as cultured cells. JCT has two cleavaged sites by Hinc II and Pvu II digestion, repectively, which were not described in the other strains. This seemed to be adventagious for JCT to widen the host range.
3. Differences of regulatory gene of JCT: We examined the DNA sequences of the regulatory genes of JCT, and compared them with other JC viruses. JCT has 23-base pair insertion after TATA sequences. The insertion, which has not detected in the other , has a potential core sequence of the enhancer. Thus, the high oncogenicity of JCT may owe this insertion of enhancer DNA in its regulatory gene.
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