title: Mice expressing RHAG and RHD human blood group genes.
abstract: Anti-RhD prophylaxis of haemolytic disease of the fetus and newborn (HDFN) is highly effective, but as the suppressive mechanism remains uncertain, a mouse model would be of interest. Here we have generated transgenic mice expressing human RhAG and RhD erythrocyte membrane proteins in the presence and, for human RhAG, in the absence, of mouse Rhag. Human RhAG associates with mouse Rh but not mouse Rhag on red blood cells. In Rhag knockout mice transgenic for human RHAG, the mouse Rh protein is "rescued" (re-expressed), and co-immunoprecipitates with human RhAG, indicating the presence of hetero-complexes which associate mouse and human proteins. RhD antigen was expressed from a human RHD gene on a BAC or from RHD cDNA under control of β-globin regulatory elements. RhD was never observed alone, strongly indicative that its expression absolutely depends on the presence of transgenic human RhAG. This first expression of RhD in mice is an important step in the creation of a mouse model of RhD allo-immunisation and HDFN, in conjunction with the Rh-Rhag knockout mice we have developed previously.
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France ; Inserm UMR_S 665, Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, UMR-S665, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Goossens
authors.forename: Nelly
authors.initials: N
authors.lastname: da Silva
authors.forename: Sylvain
authors.initials: S
authors.lastname: Metral
authors.forename: Ulrich
authors.initials: U
authors.lastname: Cortes
authors.forename: Isabelle
authors.initials: I
authors.lastname: Callebaut
authors.forename: Julien
authors.initials: J
authors.lastname: Picot
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mouro-Chanteloup
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cartron
mesh_terms: D064751:Ammonium Compounds / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055503:Protein Multimerization; D012204:Rh-Hr Blood-Group System / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D055544:beta-Globins / Q000378:metabolism
chemical_list: D064751:Ammonium Compounds; D001798:Blood Proteins; D027682:Cation Transport Proteins; D008562:Membrane Glycoproteins; C498523:RHAG protein, human; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen; D055544:beta-Globins