Tissue-specific expression and regulation of the mitogen-regulated protein genes

Mitogen Regulated Protein (MRP; also called Proliferin; or MRP/PLF) is a member of the Prolactin/Growth Hormone gene family. There is evidence that MRP/PLF is a uterine growth factor and an angiogenesis factor. Between four and six highly homologous MRP/PLF genes (mrp/plf ) exist in the mouse, but the significance of multiple genes has not been determined. MRP/Plf is produced at high levels during mid-gestation by the placenta, where expression is restricted to the trophoblastic giant cells. To better understand the regulation of the mrp/ plf genes in vivo, we have developed an assay to analyze the temporal expression pattern of different mrp/plf genes during gestation. We identified mrp/plf3 as the major placental mrp/plf during gestation, and also identified and cloned a new mrp/plf (mrp/plf4), which has a different temporal expression profile than mrp/plf3. We further investigated the spatial expression of mrp/plf genes in vivo and found that different mrp/plf genes have distinct expression patterns in the adult mouse. Mrp/ plf4 is the major mrp/plf in the skin of ears and tail, plf1 is the major mrp/ plf of the epithelia of the gastrointestinal tract, and mrp/plf3 is expressed by keratinocytes during wound healing and the hair follicle cycle.; Further studies were done to define elements involved in tissue specific expression of the mrp/plf3 gene. 1.5kb of 5′ sequence and 3kb of 3′ sequence are able to drive lacZ reporter gene expression in transiently transfected cells, but are unable to direct detectable tissue specific expression in transgenic embryos or mice. However, if a heterologous and ubiquitously active enhancer (hCMV) is added to these sequences, giant cell and wound or hair follicle keratinocyte transgene expression is observed. This suggests that the mrp/plf3 surrounding sequences contain the information required for directing tissue specific expression, but lack other undefined elements necessary for producing detectable expression when integrated into chromatin in vivo.