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

Nat Immunol. 2005 Jan;6(1):49-56. doi: 10.1038/ni1146. Epub 2004 Nov 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / immunology*
  • Anemia / metabolism
  • Animals
  • Apoptosis / immunology
  • Apoptosis / physiology*
  • DNA / metabolism*
  • Embryo Loss / genetics
  • Embryo Loss / metabolism*
  • Endodeoxyribonucleases / deficiency
  • Endodeoxyribonucleases / genetics
  • Gene Expression Regulation
  • Interferon-beta / metabolism*
  • Liver / embryology
  • Liver / metabolism
  • Macrophages / metabolism
  • Mice
  • RNA, Messenger / biosynthesis


  • RNA, Messenger
  • Interferon-beta
  • DNA
  • Endodeoxyribonucleases
  • deoxyribonuclease II