title: Embryonic lethality and fetal liver apoptosis in mice lacking all three small Maf proteins.
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.
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Fumiki
authors.initials: F
authors.lastname: Katsuoka
authors.forename: Hozumi
authors.initials: H
authors.lastname: Motohashi
authors.forename: James Douglas
authors.initials: JD
authors.lastname: Engel
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005313:Fetal Death; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D008099:Liver / Q000196:embryology* / Q000378:metabolism; D051260:MafF Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051259:MafG Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D050985:MafK Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D012097:Repressor Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D051260:MafF Transcription Factor; D051259:MafG Transcription Factor; D050985:MafK Transcription Factor; C484146:Maff protein, mouse; C491247:Mafg protein, mouse; C494696:Mafk protein, mouse; D009687:Nuclear Proteins; D012097:Repressor Proteins