Gene Targeting Study Reveals Unexpected Expression of Brain-expressed X-linked 2 in Endocrine and Tissue Stem/Progenitor Cells in Mice

Background: The role and precise expression pattern of individual brain-expressed X-linked genes in vivo were unknown. Results: Bex2-EGFP knock-in-knock-out mice were viable and fertile. Outside the brain, EGFP was expressed in specific cell populations. Conclusion: Bex2 plays redundant roles in vivo but is specifically expressed in endocrine and stem/progenitor cells. Significance: Bex2 is a novel marker for endocrine and stem/progenitor cells. Identification of genes specifically expressed in stem/progenitor cells is an important issue in developmental and stem cell biology. Genome-wide gene expression analyses in liver cells performed in this study have revealed a strong expression of X-linked genes that include members of the brain-expressed X-linked (Bex) gene family in stem/progenitor cells. Bex family genes are expressed abundantly in the neural cells and have been suggested to play important roles in the development of nervous tissues. However, the physiological role of its individual members and the precise expression pattern outside the nervous system remain largely unknown. Here, we focused on Bex2 and examined its role and expression pattern by generating knock-in mice; the enhanced green fluorescence protein (EGFP) was inserted into the Bex2 locus. Bex2-deficient mice were viable and fertile under laboratory growth conditions showing no obvious phenotypic abnormalities. Through an immunohistochemical analysis and flow cytometry-based approach, we observed unique EGFP reporter expression patterns in endocrine and stem/progenitor cells of the liver, pyloric stomach, and hematopoietic system. Although Bex2 seems to play redundant roles in vivo, these results suggest the significance and potential applications of Bex2 in studies of endocrine and stem/progenitor cells.