Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice

Diann M. McCoy, Kurt Fisher, John Robichaud, Alan J. Ryan, Rama K. Mallampalli

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Lung development is associated with a surge in surfactant phosphatidylcholine (PC) production to prepare the newborn for extrauterine breathing. This process is associated with a marked increase in the activity of the rate-regulatory surfactant enzyme, CTP:phosphocholine cytidylyltransferase (CCTα). To investigate the molecular basis for developmental activation of CCTα, we analyzed expression of endogenous CCTα and a reporter gene, β-galactosidase, in fetal, newborn, and adult promoter-reporter transgenic mice. Transgenics harboring ∼2 kb of the CCTα promoter linked upstream of a β-galactosidase reporter gene displayed relatively high expression in distal lung epithelia. Endogenous lung CCTα and β-galactosidase activities, protein content, and transcript levels displayed maximal expression within the newborn period. CCTα and β-galactosidase activities and enzyme levels increased with time in cultured fetal lung explants isolated from transgenics. Transfectional analysis using CCTα promoter-reporter constructs in developing rat type II cells revealed that a region encompassing -169/+71 contained the DNA elements required for perinatal activation. The studies demonstrate that developmental induction of surfactant phospholipid is due, at least in part, to transcriptional activation of the CCTα gene.

Original languageEnglish (US)
Pages (from-to)394-402
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume35
Issue number3
DOIs
StatePublished - Sep 2006
Externally publishedYes

Keywords

  • Development
  • Pulmonary
  • Surfactant

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of 'Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice'. Together they form a unique fingerprint.

Cite this