First Author | Kawane K | Year | 2003 |
Journal | Nat Immunol | Volume | 4 |
Issue | 2 | Pages | 138-44 |
PubMed ID | 12524536 | Mgi Jnum | J:81474 |
Mgi Id | MGI:2449392 | Doi | 10.1038/ni881 |
Citation | Kawane K, et al. (2003) Impaired thymic development in mouse embryos deficient in apoptotic DNA degradation. Nat Immunol 4(2):138-44 |
abstractText | Apoptosis is often accompanied by the degradation of chromosomal DNA. Caspase-activated DNase (CAD) is an endonuclease that is activated in dying cells, whereas DNase II is present in the lysosomes of macrophages. Here, we show that CAD(-/-) thymocytes did not undergo apoptotic DNA degradation. But, when apoptotic cells were phagocytosed by macrophages, their DNA was degraded by DNase II. The thymus of DNase II(-/-)CAD(-/-) embryos contained many foci carrying undigested DNA and the cellularity was severely reduced due to a block in T cell development. The interferon-beta gene was strongly up-regulated in the thymus of DNase II(-/-)CAD(-/-) embryos, suggesting that when the DNA of apoptotic cells is left undigested, it can activate innate immunity leading to defects in thymic development. |