Mice lacking the CARD of CARMA1 exhibit defective B lymphocyte development and impaired proliferation of their B and T lymphocytes.
CARMA1 (originally called CARD11) is a membrane-associated guanylate kinase family member that is required for T cell receptor (TCR)-induced NF-kappa B activation in T cell leukemia lines. It uses its N-terminal caspase activation and recruitment domain (CARD) to interact with the CARD in the downstream adaptor Bcl-10. We show that primary B and T lymphocytes from knock-in mice expressing only a CARDless form of CARMA1 (Delta CARD) are defective at mitogen-induced NF-kappa B activation and fail to proliferate. CARMA1 mutant mice exhibited normal T but impaired B cell development; CD5(+) peritoneal B cells were absent, and serum immunoglobulin levels were markedly reduced. A lacZ reporter gene knocked into the CARMA1 locus confirmed lymphocyte-specific expression of CARMA1. Thus, CARMA1 has an essential role in mediating B and T lymphocyte proliferation and requires its CARD to engage downstream signaling components.
Newton
Kim
K
Molecular Oncology Department, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
Dixit
Vishva M
VM
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D015139:Blotting, Southern; D015153:Blotting, Western; D002874:Chromosome Mapping; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D051528:Guanylate Kinases; D007763:Lac Operon / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000276:immunology* / Q000378:metabolism*; D011233:Precipitin Tests; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
D016328:NF-kappa B; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases