Related Experiment Video
Updated: Aug 9, 2026
11:48
Genetic Manipulation of the Mouse Developing Hypothalamus through In utero Electroporation
Published on: July 24, 2013
Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA
Hideyuki Yoshida1, Yasutaka Okabe, Kohki Kawane
1Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Nature Immunology
|November 30, 2004
Summary
DNase II deficiency causes embryonic lethality due to undigested DNA triggering interferon-beta production. Blocking the type I interferon receptor in double-mutant mice rescues this embryonic lethality, identifying a key pathway.
Area of Science:
- Developmental biology
- Immunology
- Genetics
Background:
- DNase II-deficient mouse embryos exhibit lethality in utero.
- Accumulation of undigested DNA in macrophages is observed in these embryos.
Purpose of the Study:
- To investigate the mechanism of embryonic lethality in DNase II-deficient mice.
- To identify the role of interferon-beta in DNase II-deficient embryonic lethality.
Main Methods:
- Generation of DNase II-deficient and type I interferon receptor-deficient double-mutant mice.
- Analysis of apoptosis, DNA degradation, and gene expression in embryonic livers.
- Assessment of embryonic survival and interferon-responsive gene regulation.
Main Results:
- Erythroid precursor cell apoptosis and undigested DNA accumulation in DNase II-deficient embryonic livers.
- Interferon-beta mRNA expression by resident macrophages in DNase II-deficient livers.
- Rescue of embryonic lethality in double-mutant mice lacking DNase II and type I interferon receptor.
Conclusions:
- DNase II deficiency leads to DNA accumulation, triggering interferon-beta production.
- Interferon-beta induces specific interferon-responsive genes, causing embryonic lethality.
- Targeting the interferon pathway can overcome DNase II-deficiency-related embryonic lethality.
