Bad-deficient mice develop diffuse large B cell lymphoma

Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9324-9. doi: 10.1073/pnas.1533446100. Epub 2003 Jul 22.

Abstract

The proapoptotic activity of the "BH3-only" molecule BAD can be differentially regulated by survival factor signaling. Bad-deficient mice lacking both BAD long and BAD short proteins proved viable, and most cell types appeared to develop normally. BAD did not exclusively account for cell death after withdrawal of survival factors, but it was an intermediate for epidermal growth factor- or insulin-like growth factor I-countered apoptosis, consistent with a "sensitizing" BH3-only molecule. Lymphocytes developed normally with no premalignant hyperplasia, but they displayed subtle abnormalities in proliferation and IgG production. Despite the minimal phenotype, Bad-deficient mice progressed, with aging, to diffuse large B cell lymphoma of germinal center origin. Exposure of Bad-null mice to sublethal gamma-irradiation resulted in an increased incidence of pre-T cell and pro-/pre-B cell lymphoblastic leukemia/lymphoma. Thus, proapoptotic BAD suppresses tumorigenesis in the lymphocyte lineage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • B-Lymphocytes / metabolism
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology*
  • Cell Death
  • Cell Lineage
  • DNA, Complementary / metabolism
  • Exons
  • Gamma Rays
  • Immunoglobulin G
  • Karyotyping
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Genetic
  • Nucleic Acid Hybridization
  • Phenotype
  • Protein Biosynthesis
  • Signal Transduction
  • T-Lymphocytes / metabolism
  • Transcription, Genetic
  • bcl-Associated Death Protein

Substances

  • Bad protein, mouse
  • Carrier Proteins
  • DNA, Complementary
  • Immunoglobulin G
  • bcl-Associated Death Protein