Bax deficiency extends the survival of ku70 knockout mice that develop lung and heart diseases

J. Ngo, M. Matsuyama, C. Kim, I. Poventud-Fuentes, A. Bates, S. L. Siedlak, H. G. Lee, Y. Q. Doughman, M. Watanabe, A. Liner, B. Hoit, N. Voelkel, S. Gerson, P. Hasty, S. Matsuyama

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Ku70 (Lupus Ku autoantigen p70) is essential in nonhomologous end joining DNA double-strand break repair, and ku70−/− mice age prematurely because of increased genomic instability and DNA damage responses. Previously, we found that Ku70 also inhibits Bax, a key mediator of apoptosis. We hypothesized that Bax-mediated apoptosis would be enhanced in the absence of Ku70 and contribute to premature death observed in ku70−/− mice. Here, we show that ku70−/− bax+/ − and ku70−/− bax−/− mice have better survival, especially in females, than ku70−/− mice, even though Bax deficiency did not decrease the incidence of lymphoma observed in a Ku70-null background. Moreover, we found that ku70−/− mice develop lung diseases, like emphysema and pulmonary arterial (PA) occlusion, by 3 months of age. These lung abnormalities can trigger secondary health problems such as heart failure that may account for the poor survival of ku70−/− mice. Importantly, Bax deficiency appeared to delay the development of emphysema. This study suggests that enhanced Bax activity exacerbates the negative impact of Ku70 deletion. Furthermore, the underlying mechanisms of emphysema and pulmonary hypertension due to PA occlusion are not well understood, and therefore ku70−/− and Bax-deficient ku70−/− mice may be useful models to study these diseases.

Original languageEnglish (US)
Article numbere1706
Pages (from-to)1-12
Number of pages12
JournalCell Death and Disease
Volume6
Issue number3
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Bax deficiency extends the survival of ku70 knockout mice that develop lung and heart diseases'. Together they form a unique fingerprint.

  • Cite this

    Ngo, J., Matsuyama, M., Kim, C., Poventud-Fuentes, I., Bates, A., Siedlak, S. L., Lee, H. G., Doughman, Y. Q., Watanabe, M., Liner, A., Hoit, B., Voelkel, N., Gerson, S., Hasty, P., & Matsuyama, S. (2015). Bax deficiency extends the survival of ku70 knockout mice that develop lung and heart diseases. Cell Death and Disease, 6(3), 1-12. [e1706]. https://doi.org/10.1038/cddis.2015.11