Mice lacking the CARD of CARMA1 exhibit defective B lymphocyte development and impaired proliferation of their B and T lymphocytes

Curr Biol. 2003 Jul 15;13(14):1247-51. doi: 10.1016/s0960-9822(03)00458-5.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Blotting, Southern
  • Blotting, Western
  • Chromosome Mapping
  • Flow Cytometry
  • Gene Expression Regulation
  • Guanylate Kinases
  • Lac Operon / physiology
  • Mice
  • Mice, Mutant Strains
  • NF-kappa B / metabolism*
  • Nucleoside-Phosphate Kinase / immunology*
  • Nucleoside-Phosphate Kinase / metabolism*
  • Precipitin Tests
  • Signal Transduction*
  • T-Lymphocytes / metabolism*

Substances

  • NF-kappa B
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases