Functional analysis of cell adhesion molecule, JAM-4S, specifically expressed in tissue specific stem cells.

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In this project, we focused on the analysis of molecule(s), especially cell surface molecule(s), which are commonly expressed in several tissue specific stem cells because tissue specific stem cells show quite similar properties. Then, we have cloned one of the cell adhesion molecules, JAM-4, which are expressed in both hematopoietic stem cells and male germ stem cells.The JAM-4 transcript, named JAM-4S, which we have cloned from stem cells is shorter than that cloned from kidney and lung. The transcript encoded an isoform of JAM-4 protein, which only contain one immunoglobulin domain. Therefore, we analyzed the function of JAM-4S protein as well as JAM-4 protein in the stem cells at male reproduction system and hematopoietic system. In testes, JAM-4S is expressed in gonocytes and spermatogonia at neonatal stage. In hematopoietic system, JAM-4S is expressed in both stem cell-and progenitor-populations in bone marrow cells.In order to understand the biological function in vivo, we have generated the JAM-4 deficient mice. Because it is difficult to generate JAM-4S specific knock out mice, we have generated conventional JAM-4 knock out mice. The JAM-4 deficient mice alive at least 2 years so far and do not show obvious abnormality. The testes specimen of JAM-4 deficient mice showed normal development. The hematopoiesis of the JAM-4 deficient mice was also normal. In testes and bone marrow, the family molecules of JAM-4, such as JAM-A and JAM-B are also expressed. Therefore, we are going to generate JAM-B/JAM-4-double knock out mice to analyze the phenotype on stem cell population.