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Publication : Impaired thymic development in mouse embryos deficient in apoptotic DNA degradation.

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.
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