Related Experiment Videos
Rescue of embryonic lethality in hepatocyte growth factor/scatter factor knockout mice
Abstract:
While the targeted disruption of a gene is a powerful tool for investigating the physiological functions of that gene, disruption of a gene essential for embryogenesis leads to embryonic death. Rescue of the defect(s) causing embryonic death should promote survival, thus permitting further evaluation of the roles that the gene plays later in the developmental process. Disruption of the gene for mouse hepatocyte growth factor/scatter factor (HGF/SF) leads to middle-stage embryonic lethality because of a defect in placental development. Here we report that a single injection of HGF/SF at embryonic day 9.5 (E9.5) into the amniotic cavity of HGF/SF(-/-) embryos rescued the placental defect and resulted in the survival of the embryos until term. Histological analysis suggested that HGF/SF is also required at the late stage of development for tissue organogenesis. Thus, injection of a secreted factor can be a useful method to rescue the defects causing embryonic lethality.
Insights
Targeted gene disruption can cause embryonic death. Injecting hepatocyte growth factor/scatter factor (HGF/SF) into HGF/SF(-/-) embryos rescued placental defects, allowing survival to term.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Gene disruption is crucial for understanding gene function, but essential genes can cause embryonic lethality.
- Investigating the roles of essential genes requires methods to overcome embryonic lethality.
- Hepatocyte growth factor/scatter factor (HGF/SF) gene disruption leads to embryonic death due to placental defects.
Discussion:
- A single injection of HGF/SF into HGF/SF(-/-) embryos at embryonic day 9.5 rescued placental development.
- This intervention enabled embryo survival until term, overcoming the previously observed embryonic lethality.
- Histological analysis indicates HGF/SF is also vital for late-stage tissue organogenesis.
Key Insights:
- HGF/SF is essential for both early placental development and later tissue organogenesis.
- Direct injection of a secreted factor can rescue genetic defects causing embryonic lethality.
- This rescue strategy allows for the study of genes essential for embryogenesis.
Outlook:
- The described injection method offers a novel approach to study essential genes in developmental processes.
- Further research can explore the therapeutic potential of HGF/SF in developmental disorders.
- This technique may be applicable to other gene-disruption models with embryonic lethality.