Phenotypic consequences of lung-specific inducible expression of FGF-3

Proceedings of the National Academy of Sciences of the United States of America
B ZhaoF J DeMayo

Abstract

Members of the fibroblast growth factor (FGF) family play a critical role in embryonic lung development and adult lung physiology. The in vivo investigation of the role FGFs play in the adult lung has been hampered because the constitutive pulmonary expression of these factors often has deleterious effects and frequently results in neonatal lethality. To circumvent these shortcomings, we expressed FGF-3 in the lungs under the control of the progesterone antagonist-responsive binary transgenic system. Four binary transgenic lines were obtained that showed ligand-dependent induction of FGF-3 with induced levels of FGF-3 expression dependent on the levels of expression of the GLp65 regulator as well as the dose of the progesterone antagonist, RU486, administered. FGF-3 expression in the adult mouse lung resulted in two phenotypes depending on the levels of induction of FGF-3. Low levels of FGF-3 expression resulted in massive free alveolar macrophage infiltration. High levels of FGF-3 expression resulted in diffuse alveolar type II cell hyperplasia. Both phenotypes were reversible after the withdrawal of RU486. This system will be a valuable means of investigating the diverse roles of FGFs in the adult lung.

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Citations

Dec 3, 2002·Current Opinion in Biotechnology·Jeffrey L Nordstrom
Sep 12, 2001·Trends in Endocrinology and Metabolism : TEM·F J DeMayo, S Y Tsai
Sep 21, 2002·Seminars in Cell & Developmental Biology·Elly S W NganSophia Y Tsai
Jan 20, 2004·Genes & Development·Maranke I KosterDennis R Roop
Feb 24, 2004·Annual Review of Physiology·I KwakF J DeMayo
Aug 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Elly S W NganSophia Y Tsai
Oct 12, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Jinger XieTerry W Hermiston
Sep 3, 2002·Mechanisms of Development·Jeiwook ChaeRobert M Grainger
Oct 4, 2011·Neurobiology of Disease·Ami MankodiCharles A Thornton
Jun 12, 2008·Developmental Biology·Alexander Emelyanov, Serguei Parinov
Nov 18, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Isamu HokutoJeffrey A Whitsett
Apr 3, 2002·The Journal of Biological Chemistry·Jeffrey A WhitsettMildred T Stahlman
Sep 28, 2002·Molecular Endocrinology·Norio TakamotoFrancesco J DeMayo
Mar 18, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kristin R MeltonTimothy E Weaver
Mar 17, 2005·Genes & Development·Ralph Meuwissen, Anton Berns

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