Gene targeting study reveals unexpected expression of brain-expressed X-linked 2 in endocrine and tissue stem/progenitor cells in mice

J Biol Chem. 2014 Oct 24;289(43):29892-911. doi: 10.1074/jbc.M114.580084. Epub 2014 Aug 20.

Abstract

Identification of genes specifically expressed in stem/progenitor cells is an important issue in developmental and stem cell biology. Genome-wide gene expression analyses in liver cells performed in this study have revealed a strong expression of X-linked genes that include members of the brain-expressed X-linked (Bex) gene family in stem/progenitor cells. Bex family genes are expressed abundantly in the neural cells and have been suggested to play important roles in the development of nervous tissues. However, the physiological role of its individual members and the precise expression pattern outside the nervous system remain largely unknown. Here, we focused on Bex2 and examined its role and expression pattern by generating knock-in mice; the enhanced green fluorescence protein (EGFP) was inserted into the Bex2 locus. Bex2-deficient mice were viable and fertile under laboratory growth conditions showing no obvious phenotypic abnormalities. Through an immunohistochemical analysis and flow cytometry-based approach, we observed unique EGFP reporter expression patterns in endocrine and stem/progenitor cells of the liver, pyloric stomach, and hematopoietic system. Although Bex2 seems to play redundant roles in vivo, these results suggest the significance and potential applications of Bex2 in studies of endocrine and stem/progenitor cells.

Keywords: Brain-expressed X-linked Gene; Development; Endocrine Cells; Gene Expression; Gene Knock-out; Hematopoietic Stem Cells; Liver; Stem Cells; X-linked Gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Lineage / genetics
  • Cell Proliferation
  • Endocrine Cells / cytology
  • Endocrine Cells / metabolism*
  • Endoderm / cytology
  • Female
  • Fetus / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Targeting*
  • Genes, Reporter
  • Genetic Loci
  • Green Fluorescent Proteins / metabolism
  • Hematopoiesis / genetics
  • Liver / embryology
  • Liver / metabolism
  • Male
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Organ Specificity
  • Phenotype
  • Promoter Regions, Genetic / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription, Genetic

Substances

  • Bex2 protein, mouse
  • Biomarkers
  • Nerve Tissue Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins