Mice lacking all conventional MHC class II genes

MHC class II (MHC-II) molecules play a central role in the selection of the T cell repertoire, in the establishment and regulation of the adaptive imm une response, and in autoimmune deviation. We have generated knockout mice lacking all four of the classical murine MHC-II. genes (MHCIIDelta/Delta mi ce), via a large (80-kilobase) deletion of the entire class II region that was engineered by homologous recombination and Cre recombinase-mediated exc ision, These mice feature immune system perturbations like those of Aar and AP knockout animals, notably a dearth of CD4(+) lymphocytes in the thymus and spleen. No new anatomical or physiological abnormalities were observed in MHCIIDelta/Delta mice. Because these animals are devoid of all classical MNC-II chains, even unpaired chains, they make excellent recipients for MH C-II transgenes from other species, avoiding the problem of interspecies cr oss-pairing of MHC-II chains. Therefore, they should be invaluable for engi neering "humanized" mouse models of human MHC-LI-associated autoimmune diso rders.