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 immune response, and in autoimmune deviation. We have generated knockout mice lacking all four of the classical murine MHC-II genes (MHCII(Delta/Delta) mice), via a large (80-kilobase) deletion of the entire class II region that was engineered by homologous recombination and Cre recombinase-mediated excision. These mice feature immune system perturbations like those of Aalpha and Abeta knockout animals, notably a dearth of CD4(+) lymphocytes in the thymus and spleen. No new anatomical or physiological abnormalities were observed in MHCII(Delta/Delta) mice. Because these animals are devoid of all classical MHC-II chains, even unpaired chains, they make excellent recipients for MHC-II transgenes from other species, avoiding the problem of interspecies cross-pairing of MHC-II chains. Therefore, they should be invaluable for engineering "humanized" mouse models of human MHC-II-associated autoimmune disorders.
Madsen
L
L
Department of Clinical Immunology, Rigshospitalet, 2200 Copenhagen, Denmark.
Labrecque
N
N
Engberg
J
J
Dierich
A
A
Svejgaard
A
A
Benoist
C
C
Mathis
D
D
Fugger
L
L
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D002872:Chromosome Deletion; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D019426:Integrases; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D013234:Stem Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014764:Viral Proteins
D000949:Histocompatibility Antigens Class II; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases