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English

Lethal anemia caused by interferon-β produced in mouse embryos carrying undigested DNA.

論文誌情報 Nat Immunol 6, 49-56 (2005)
著者 Yoshida H, Okabe Y, Kawane K, Fukuyama H, Nagata S.
論文タイトル Lethal anemia caused by interferon-β produced in mouse embryos carrying undigested DNA.
PubMed 15568025

Figure1. Apoptotic cell death of fetal ...

要旨

The livers of DNase II-deficient mouse embryos contain many macrophages carrying undigested DNA, and the embryos die in utero. Here we report that erythroid precursor cells underwent apoptosis in the livers of DNase II-deficient embryos and that in the liver, interferon-beta mRNA was expressed by the resident macrophages. When the DNase II-deficient mice were crossed with mice deficient in type I interferon receptor, the resultant 'double-mutant' mice were born healthy. The double-mutant embryos expressed interferon-beta mRNA, but the expression of a subset of the interferon-responsive genes dysregulated in DNase II-deficient embryos was restored to normal. These results indicate that the inability to degrade DNA derived from erythroid precursors results in interferon-beta production that induces expression of a specific set of interferon-responsive genes associated with embryonic lethality in DNase II-deficient mice.

Nagata2005-2.jpg Nagata2005.jpg Figure1. Apoptotic cell death of fetal liver cells in Dnase2a-/- embryos.
(a) Histochemical analysis of fetal liver. Liver sections from E14.5 Dnase2a+/+ (WT) and Dnase2a-/- (DNase II KO) embryos were stained using TUNEL. Scale bar, 100 m.