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Cloning and characterization of a novel developmentally regulated gene in the fetal lung

We are interested in genes that regulate lung development in late gestation. Using a probe identified by differential display-PCR, we cloned a 3.1 kb cDNA LGL1 (AF109674) encoding a deduced polypeptide of 480 amino acids. Northern blot analysis showed that LGL1 is induced by glucocorticoid and is expressed in fetal lung adjacent fibroblasts but not in the epithelium. LGL1 is detectable in fetal rat heart, kidney and intestine, and is conserved across human, rat and mouse adult lungs. RT-PCR analysis detected LGL1 expression in human fetal lung, kidney, heart and intestine. In situ hybridization studies demonstrated that LGL1 expression is restricted to the mesenchyme, while FISH mapped LGL1 to human chromosome 16824. LGL1 demonstrated homology to P25TI, a polypeptide with weak trypsin inhibitor activity, as well as the CRISP family of androgen-regulated, cysteine rich secretory proteins. We expressed a hexahistidine tagged LGL1 in an E. coli expression system in order to facilitate characterization of the protein and determine its role in fetal lung maturation. The data gathered thus far are consistent with LGL1 having a role in lung development via the regulation of extracellular matrix degradation.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33010
Date January 2000
CreatorsKassamali, Ferhat Q.
ContributorsKaplan, Feige (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Department of Human Genetics.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001838271, proquestno: MQ75324, Theses scanned by UMI/ProQuest.

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