Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA.
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.
Yoshida
Hideyuki
H
Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Okabe
Yasutaka
Y
Kawane
Kohki
K
Fukuyama
Hidehiro
H
Nagata
Shigekazu
S
D000740:Anemia / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D004247:DNA / Q000378:metabolism*; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000172:deficiency / Q000235:genetics; D005786:Gene Expression Regulation; D016899:Interferon-beta / Q000378:metabolism*; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis
D012333:RNA, Messenger; D016899:Interferon-beta; D004247:DNA; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II