Tissue- and developmental stage-specific activation of α5 and α6(IV) collagen expression in the upper gastrointestinal tract of transgenic mice

Christine Herzog, Liyan Zhuang, Lucian Gorgan, Yoav Segal, Jing Zhou

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Little is known about mechanisms regulating gene expression for the α chains of basement membrane type IV collagen, arranged head-to-head in transcription units COL4A1-COL4A2, COL4A3-COL4A4, and COL4A5-COL4A6, and implicated broadly in genetic diseases. To investigate these mechanisms, we generated transgenic mouse lines bearing 5′-flanking sequences of COL4A5 and COL4A6, cloned upstream of a lacZ reporter gene. A 3.8-kb fragment upstream of COL4A6 directs reporter gene expression in the esophagus, stomach, and duodenum, whereas a 13.8-kb fragment directs expression in the esophagus only. A 10.6-kb fragment upstream of COL4A5 directs expression in the esophagus. Coupled with evidence of long-range conservation between human and mouse non-coding sequences, described herein, our findings provide the first indication that highly specialized patterns characteristic of COL4A5-COL4A6 expression in vivo arise from effects of distributed cis-acting regulatory elements on a bidirectional proximal promoter, itself transcriptionally competent.

Original languageEnglish (US)
Pages (from-to)553-560
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume311
Issue number2
DOIs
StatePublished - Nov 14 2003

Keywords

  • Collagen type IV
  • Esophagus
  • Gastric mucosa
  • Gene expression regulation
  • Intestinal mucosa
  • Mice, transgenic
  • Nephritis, hereditary

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