Generation of mice expressing human RHAG and RHD blood group genes

Abstract

Anti‐RhD prophylaxis of haemolytic disease of the fetus and newborn (HDFN) is highly effective, but since the suppressive mechanism remains uncertain, a mouse model of this pathology would be useful to achieve a better understanding of the processes involved. A number of highly interesting models of mice transgenic for human blood groups, producing alloantibodies through transfusion, and even pregnancy, have been developed in recent years. Expression of RhD has, however, proved difficult in mice, due to its integration into a membrane complex, a heterotrimer involving not only Rh, but also its RhAG protein partner. In our experience, RhD could be expressed from a human RHD gene on a BAC or from RHD cDNA under control of β‐globin regulatory elements, but RhD erythrocyte membrane expression was obtained only in mice transgenic for both the RHAG and RHD human genes. We here give an overview of our approach to the generation of transgenic mice co‐expressing human RhAG and RhD erythrocyte membrane proteins, and discuss further challenges to be resolved in the quest for a model of RhD alloimmunisation and HDFN.