Embryonic lethality and fetal liver apoptosis in mice lacking all: Three small Maf proteins

Hiromi Yamazaki, Fumiki Katsuoka, Hozumi Motohashi, James Douglas Engel, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)808-816
Number of pages9
JournalMolecular and cellular biology
Issue number4
Publication statusPublished - 2012 Feb

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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