In vitro reconstruction of tissue function with the immortalized cell lines from transgenic mouse

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To reconstruct the tissue functions in vitro with the immortal tissue cell lines, we established several immortalized cell lines with differentiated functions from the temperature-sensitive SV40 large T-antigen gene (ts T) transgenic mice.By coculturing the hematopoietic stem cells with the bone marrow stromal cell lines established form the ts T transgenic mice, 4 novel immature hematopoietic stem cell-like cell lines including were established. THS119 cell line exhibited Lin-, c-Kit+ Sca-1+ surface phenotype similar to bone marrow hematopoietic stem cells. B31-1 cell line show properties of B-lymphoid progenitors. DFC cells were generated from Dexter type bone marrow culture and DFC-a, a clonal isolate, showed the phenotype similar to bipotent myeloid progenitor cells and DFC-28 showed very early lymphoid progenitor cells. All cell lines required stromal cells for their maintenance.Using these coculture systems, genes for 2 new membrane proteins (SMAP-1 and CD47/IAP), and a new cytoskeletal protein (mys-PDZ) were cloned and their function was examined.In addition, novel endothelial cell lines from blood-brain barrier, adrenal gland cell lines, and brain astrocyte cell lines were established from the ts T-transgenic mice.Recently, ts T-transgenic rats were generated and the immortlised cell lines with specialized tissue functions such as hepatocytes, kidney tubule cell lines, and novel endothelial cell lines from several tissue-blood barriers were established.