Mrj encodes a DnaJ-related co-chaperone that is essential for murine placental development

We have identified a novel gene in a gene trap screen that encodes a protei n related to the DnaJ co-chaperone in E. coli, The gene, named Mrj (mammali an relative of DnaJ) was expressed throughout development in both the embry o and placenta. Within the placenta, expression was particularly high in tr ophoblast giant cells but moderate levels were also observed in trophoblast cells of the chorion at embryonic day 8.5, and later in the labyrinth whic h arises from the attachment of the chorion to the allantois (a process cal led chorioallantoic fusion), Insertion of the ROSA beta geo gene trap vecto r into the Mrj gene created a null allele, Homozygous Mrj mutants died at m id-gestation due to a failure of chorioallantoic fusion at embryonic day 8. 5, which precluded formation of the mature placenta. At embryonic day 8.5, the chorion in mutants was morphologically normal and expressed the cell ad hesion molecule alpha 4 integrin that is known to be required for chorioall antoic fusion, However, expression of the chorionic trophoblast-specific tr anscription factor genes Err2 and Gcm1 was significantly reduced. The mutan ts showed no abnormal phenotypes in other trophoblast cell types or in the embryo proper. This study indicates a previously unsuspected role for chape rone proteins in placental development and represents the first genetic ana lysis of DnaJ-related protein function in higher eukaryotes. Based on a sur vey of EST databases representing different mouse tissues and embryonic sta ges, there are 40 or more DnaJ-related genes in mammals. In addition to Mrj , at least two of these genes are also expressed in the developing mouse pl acenta. The specificity of the developmental defect in Mrj mutants suggests that each of these genes may have unique tissue and cellular activities.