Abstract
Now that the human genome project has been completed, the rationale of genome-oriented development of medicine has been stressed. Conditionally immortalized cell lines could play an important role in “post-genome” projects, as they are applicable to high throughput screening system, which enables the prompt and massive screening of lead compounds and their optimization. In this regard, clonal cells, derived from temperature-sensitive simian virus 40 large tumor antigen gene transgenic mice, are interesting. They grew at the permissive temperature (33°C), but their growth was arrested at the non-permissive temperature (39°C). Therefore, first, under the permissive condition, we could establish cell lines, which had been impossible to establish because of their character and the small quantity. Second, through a simple method like a temperature shift from 33°C to 39°C, we can also analyze gene expression profiles and their functions during the cell maturation. Finally, clonal cells derived from a T-antigen transgenic mouse, after being genetically crossed with a mutant mouse, would be utilized as the tools to examine the targeted gene function. Actually, by using vitamin D receptor gene-disrupted mice as mutants, we have established clonal bone marrow stromal cell lines and have clearly shown that 1, 25(OH)2D3 suppresses differentiation of stromal cells into adipocytes in a VDR-dependent manner.
