Related Experiment Video
Updated: May 26, 2026
Mouse Fetal Liver Culture System to Dissect Target Gene Functions at the Early and Late Stages of Terminal Erythropoiesis
Published on: September 9, 2014
Embryonic lethality and fetal liver apoptosis in mice lacking all three small Maf proteins
Hiromi Yamazaki1, Fumiki Katsuoka, Hozumi Motohashi
1Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
Abstract:
Embryogenesis is a period during which cells are exposed to dynamic changes of various intracellular and extracellular stresses. Oxidative stress response genes are regulated by heterodimers composed of Cap'n'Collar (CNC) and small Maf proteins (small Mafs) that bind to antioxidant response elements (ARE). Whereas CNC factors have been shown to contribute to the expression of ARE-dependent cytoprotective genes during embryogenesis, the specific contribution of small Maf proteins to such gene regulation remains to be fully examined. To delineate the small Maf function in vivo, in this study we examined mice lacking all three small Mafs (MafF, MafG, and MafK). The small Maf triple-knockout mice developed normally until embryonic day 9.5 (E9.5). Thereafter, however, the triple-knockout embryos showed severe growth retardation and liver hypoplasia, and the embryos died around E13.5. ARE-dependent cytoprotective genes were expressed normally in E10.5 triple-knockout embryos, but the expression was significantly reduced in the livers of E13.5 mutant embryos. Importantly, the embryonic lethality could be completely rescued by transgenic expression of exogenous MafG under MafG gene regulatory control. These results thus demonstrate that small Maf proteins are indispensable for embryonic development after E9.5, especially for liver development, but early embryonic development does not require small Mafs.
Insights
Small Maf proteins are essential for embryonic development after day 9.5, particularly for liver formation. Their absence causes growth defects and embryonic lethality, which can be rescued by MafG expression.
Area of Science:
- Developmental biology
- Molecular genetics
- Cellular stress response
Background:
- Embryogenesis involves dynamic cellular stresses.
- Oxidative stress response genes are regulated by Cap'n'Collar (CNC) and small Maf proteins binding to antioxidant response elements (ARE).
- The role of small Maf proteins in embryonic gene regulation is not fully understood.
Purpose of the Study:
- To investigate the in vivo function of small Maf proteins during embryogenesis.
- To determine the specific contribution of small Mafs to ARE-dependent gene regulation in developing embryos.
Main Methods:
- Generation and analysis of mice lacking all three small Mafs (MafF, MafG, MafK).
- Observation of embryonic development up to E13.5.
- Assessment of ARE-dependent gene expression in knockout embryos.
- Rescue experiments using transgenic MafG expression.
Main Results:
- Small Maf triple-knockout mice developed normally until E9.5.
- Post-E9.5, triple-knockout embryos exhibited severe growth retardation, liver hypoplasia, and embryonic lethality around E13.5.
- ARE-dependent gene expression was normal at E10.5 but reduced in E13.5 mutant livers.
- Transgenic MafG expression rescued embryonic lethality.
Conclusions:
- Small Maf proteins are indispensable for embryonic development beyond E9.5, especially for liver development.
- Early embryonic development (pre-E9.5) does not require small Mafs.
- MafG plays a crucial role in preventing embryonic lethality and ensuring proper liver development.
