The impact of genetic background and Bid on the phenotype of Bcl-2-deficiency in mice

Hong Min Ni, Xiaoyun Chen, Lei Chen, Daniell DiFrancesca, Hisashi Harada, Xiao Ming Yin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

How a central apoptosis mechanism could be modulated during a specific developmental or homeostatic process to comply with the specific needs of a particular tissue is poorly understood. Bcl-2 is a key anti-apoptosis regulator and its deletion resulted in multiple defects in mice, indicating its broad involvement in development and homeostasis of various tissues. We found that the severity and extensiveness of the defects could be greatly influenced by the genetic background of the mice. Hence, Bcl-2-deficient mice predominantly on C57BL/6 background had the most severe presentation with increased embryonic lethality, whereas Bcl-2-deficient mice predominantly on 129/SvJ background had a significantly minor phenotype. In particular, the 129/SvJ background could almost completely rescue the polycystic kidney disease phenotype of the Bcl-2 deficiency, resulting in normal renal functions. These observations would be consistent with the assumption that the C57BL/6 background is more pro-death while the 129/SvJ background is more pro-survival. Concurrent deletion of Bid, a BH3-only molecule, in either genetic background, could significantly increase the birth rate of the Bcl-2 deficient progenies and lessen lymphocytopenia, although the double knockout mice still developed the polycystic kidney diseases. Overall, our work indicates that the phenotype of Bcl-2 deficiency can be affected by multiple genetic elements, resulting in tissue-specific modulations of the cell death program during development and cellular homeostasis.

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalApoptosis
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2008

Fingerprint

Tissue
Phenotype
Polycystic Kidney Diseases
Apoptosis
Defects
Homeostasis
Cell death
Lymphopenia
Birth Rate
Modulation
Knockout Mice
Molecules
Cell Death
Kidney
Genetic Background

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Cite this

Ni, Hong Min ; Chen, Xiaoyun ; Chen, Lei ; DiFrancesca, Daniell ; Harada, Hisashi ; Yin, Xiao Ming. / The impact of genetic background and Bid on the phenotype of Bcl-2-deficiency in mice. In: Apoptosis. 2008 ; Vol. 13, No. 1. pp. 53-62.
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The impact of genetic background and Bid on the phenotype of Bcl-2-deficiency in mice. / Ni, Hong Min; Chen, Xiaoyun; Chen, Lei; DiFrancesca, Daniell; Harada, Hisashi; Yin, Xiao Ming.

In: Apoptosis, Vol. 13, No. 1, 01.01.2008, p. 53-62.

Research output: Contribution to journalArticle

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