Abstract:
:CTP:phosphocholine cytidylyltransferase (CT) is the rate-limiting enzyme in the biosynthesis by type II pneumocytes of phosphatidylcholine (PC), the predominant phospholipid in lung surfactant. Augmentation of endogenous CT activity might therefore result in enhanced surfactant PC production. To test this hypothesis, transgenic mice were created in which rat CT (rCT) was expressed under control of the human surfactant protein C (SP-C) promoter. Transgenic mice were identified by tail-clip PCR analysis and studies of four founder lines were initiated. Lung CT gene expression was enhanced in two transgenic founder lines relative to wild-type controls. These two transgenic lines also exhibited significantly higher levels of immunoreactive CT protein and CT activity in whole-lung homogenates and in cultured type II cell extracts. Disaturated PC (DSPC) content in whole-lung homogenates and the rate of DSPC synthesis in cultured type II cells were significantly increased in one transgenic line. However, neither the incorporation of radiolabeled precursors (choline and palmitate) into DSPC in vivo nor the cellular metabolism of DSPC differed significantly between transgenic and control mice. This transgenic model provides opportunity for further study of factors controlling surfactant phospholipid production in vivo.
journal_name
Am J Respir Cell Mol Biolauthors
Li J,Marsh JJ,Spragg RGdoi
10.1165/ajrcmb.26.6.4720keywords:
subject
Has Abstractpub_date
2002-06-01 00:00:00pages
709-15issue
6eissn
1044-1549issn
1535-4989journal_volume
26pub_type
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