title: A CD45 minigene restores regulated isoform expression and immune function in CD45-deficient mice: therapeutic implications for human CD45-null severe combined immunodeficiency.
abstract: Transgenic mice have been generated that carry a CD45 minigene under control of the human leukocyte function-associated antigen (LFA-1, CD11a) promoter. CD45-null mice carrying the transgene exhibit the lymphocyte lineage-specific isoform expression patterns of wild-type mice. Furthermore, these mice have normal thymocyte development and peripheral T-cell numbers. The proliferative ability of T cells in response to mitogens and antigen also is regained, as is B-cell responsiveness to anti-IgM. The antibody response to antigen is also restored and is similar to that of normal mice. Therefore, introduction of a functional CD45 minigene is sufficient to overcome the principal severe combined immunodeficiency (SCID)-associated defects and represents a potential route to a gene therapy for human CD45-deficent SCID.
authors.affiliation: Sidney Kimmel Cancer Center, San Diego, CA, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Virts
authors.forename: Oscar
authors.initials: O
authors.lastname: Diago
authors.forename: William C
authors.initials: WC
authors.lastname: Raschke
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007109:Immunity / Q000235:genetics*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013961:Thyroid Gland / Q000166:cytology; D014158:Transcription, Genetic; D019076:Transgenes / Q000235:genetics
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D020033:Protein Isoforms; D017493:Leukocyte Common Antigens