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

Abstract 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.