Strain-dependent perinatal lethality of Ovol1-deficient mice and identification of Ovol2 as a downstream target of Ovol1 in skin epidermis

Biochim Biophys Acta. 2007 Jan;1772(1):89-95. doi: 10.1016/j.bbadis.2006.08.012. Epub 2006 Sep 12.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Coloring Agents / pharmacokinetics
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / pharmacology
  • Epidermis / abnormalities
  • Epidermis / metabolism
  • Epidermis / pathology*
  • Fetal Death / genetics*
  • Genes, Lethal
  • Germ-Line Mutation
  • Kidney Diseases, Cystic / genetics*
  • Kidney Diseases, Cystic / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Transcription Factors / deficiency*
  • Transcription Factors / drug effects
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription Factors / pharmacology
  • Transcription, Genetic
  • Up-Regulation

Substances

  • Coloring Agents
  • DNA-Binding Proteins
  • MOVO protein, mouse
  • Ovo1 protein, mouse
  • Transcription Factors