Journal article
Bcl-2 reduces mutant rates in a transgenic lacZ reporter gene in mouse pre-B lymphocytes
Mutation research, Vol.522(1), pp.135-144
2003
DOI: 10.1016/S0027-5107(02)00309-3
PMID: 12517419
Abstract
To assess mutagenesis during early B-lymphocyte development in vitro, progenitor B cells (pre-B cells) were obtained from fetal livers of BALB/c mice and DBA/2N mice that harbored the transgenic shuttle vector, pUR288, with a
lacZ reporter gene for the determination of mutant frequencies (MFs). Differentiation-arrested pre-B cells demonstrated a marked dose-dependent increase in
lacZ mutant levels after exposure to γ-irradiation with a peak MF of 250×10
−5 at 2.5
Gy. Without genotoxic treatment, pre-B cells undergoing spontaneous differentiation into surface IgM expressing immature B cells exhibited
lacZ mutant levels of up to 95×10
−5. The mutational pattern was dominated in both experiments by illegitimate recombination mutations of
lacZ, not point mutations. Likewise, in both experiments, the enforced expression of Bcl-2 resulted in a striking reduction of
lacZ mutations. These findings indicated that mouse pre-B cells are prone to accumulate induced and self-inflicted mutations, particularly recombinations. Additionally, our studies revealed a heretofore unknown role of Bcl-2 in inhibiting mutagenesis during early B-cell development in mice.
Details
- Title: Subtitle
- Bcl-2 reduces mutant rates in a transgenic lacZ reporter gene in mouse pre-B lymphocytes
- Creators
- Klaus Felix - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, Room 2B10, Building 37, NIH, Bethesda, MD 20892-4255, USAAntonius Rolink - Basel Institute for Immunology, Basel, SwitzerlandFritz Melchers - Basel Institute for Immunology, Basel, SwitzerlandSiegfried Janz - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, Room 2B10, Building 37, NIH, Bethesda, MD 20892-4255, USA
- Resource Type
- Journal article
- Publication Details
- Mutation research, Vol.522(1), pp.135-144
- Publisher
- Elsevier B.V
- DOI
- 10.1016/S0027-5107(02)00309-3
- PMID
- 12517419
- ISSN
- 0027-5107
- eISSN
- 1873-135X
- Language
- English
- Date published
- 2003
- Academic Unit
- Pathology
- Record Identifier
- 9984083805902771
Metrics
17 Record Views