Strain-dependent perinatal lethality of Ovol1-deficient mice and identification of Ovol2 as a downstream target of Ovol1 in skin epidermis.
Ovol1 encodes a zinc finger transcriptional repressor that is downstream of the LEF1/beta-catenin complex, nuclear effectors of canonical Wnt signaling. Previous gene knockout studies performed in a 129SvxC57BL/6 mixed genetic background revealed that Ovol1-deficient mice survive to adulthood but display multiple tissue defects. In this study, we describe a C57BL/6 strain-specific reduction in perinatal survival of Ovol1 mutant mice. The perinatal lethality is accompanied by kidney epithelial cysts of embryonic onset and delayed skin barrier acquisition. Genetic analysis suggests a partial functional compensation by Ovol2 for the loss of Ovol1. The expression of Ovol2 was up-regulated in Ovol1-deficient epidermis, and Ovol1 represses the activity of Ovol2 promoter in a DNA binding-dependent manner. Collectively, these studies uncover novel functions of Ovol1 in mouse development and identify Ovol2 as a downstream target of Ovol1.
Teng
Andy
A
Department of Biological Chemistry, University of California, Irvine, CA 92697, USA.
Nair
Mahalakshmi
M
Wells
Julie
J
Segre
Julia A
JA
Dai
Xing
X
D000818:Animals; D001483:Base Sequence; D004396:Coloring Agents / Q000493:pharmacokinetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000494:pharmacology; D004817:Epidermis / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology*; D005313:Fetal Death / Q000235:genetics*; D005804:Genes, Lethal; D018095:Germ-Line Mutation; D052177:Kidney Diseases, Cystic / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic; D015854:Up-Regulation
D004396:Coloring Agents; D004268:DNA-Binding Proteins; C491431:MOVO protein, mouse; C490318:Ovo1 protein, mouse; D014157:Transcription Factors