Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice.

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 (CCTalpha). To investigate the molecular basis for developmental activation of CCTalpha, we analyzed expression of endogenous CCTalpha and a reporter gene, beta-galactosidase, in fetal, newborn, and adult promoter-reporter transgenic mice. Transgenics harboring approximately 2 kb of the CCTalpha promoter linked upstream of a beta-galactosidase reporter gene displayed relatively high expression in distal lung epithelia. Endogenous lung CCTalpha and beta-galactosidase activities, protein content, and transcript levels displayed maximal expression within the newborn period. CCTalpha and beta-galactosidase activities and enzyme levels increased with time in cultured fetal lung explants isolated from transgenics. Transfectional analysis using CCTalpha 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 CCTalpha gene.

authors

McCoy DM,Fisher K,Robichaud J,Ryan AJ,Mallampalli RK

doi

10.1165/rcmb.2005-0401OC

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

394-402

issue

3

eissn

1044-1549

issn

1535-4989

pii

2005-0401OC

journal_volume

35

pub_type

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