The intron 5/6 promoter region of the ship1 gene regulates expression in stem/progenitor cells of the mouse embryo.

The s-SHIP protein is a shorter isoform of the longer SHIP1 protein and lacks the N-terminal SH2 domain region contained in SHIP1. s-SHIP is expressed in ES cells and in enriched bone marrow stem cells, and may be controlled by a promoter within intron 5 of the ship1 gene. We therefore examined the potential specificity of promoter activity in ES cells of an intron 5/intron 6 ship1 genomic segment and its tissue specificity within transgenic mice expressing GFP from this promoter region. The results indicate that s-SHIP promoter activity is specific for ES cells in vitro and for known and presumptive stem/progenitor cells throughout embryo development of the transgenic mice. Specific GFP expression was observed in the blastocyst, primordial germ cells, thymus, arterioles, osteoblasts, and skin epidermis. The epidermis/epithelium is the progenitor for hair follicles, mammary tissue, and prostate. Interestingly, each of these latter tissues acquired a few GFP-positive cells in the course of their development from the epithelial layers, and these cells express marker proteins for stem/progenitor cells. These results identify potential stem cell populations, mark these cells for analyses in normal and cancer development, and implicate s-SHIP as an important protein in stem/progenitor cell function.