Bax deficiency extends the survival of Ku70 knockout mice that develop lung and heart diseases

• DOI: 10.1038/cddis.2015.11
• Publication Date: 2015-03-26T13:46:36Z
• Authors: 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
• Keywords: Ku70; Knockout mouse

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