title: Pulmonary hypoplasia in the connective tissue growth factor (Ctgf) null mouse.
abstract: Connective tissue growth factor (CTGF) is a mediator of growth factor activity, and Ctgf knockouts die at birth from respiratory failure due to skeletal dysplasia. Previous microarray analysis revealed Ctgf down-regulation in the hypoplastic lungs of amyogenic mouse embryos. This study, therefore, examined pulmonary development in Ctgf-/- mouse fetuses to investigate if respiration could also have been impaired by lung abnormalities. The Ctgf-/- lungs were hypoplastic, with reduced cell proliferation and increased apoptosis. PDGF-B, its receptor and IGF-I, were markedly attenuated and the TTF-1 gradient lost. Type II pneumocyte differentiation was perturbed, the cells depicting excessive glycogen retention and diminished lamellar body and nuclear size, though able to synthesize surfactant-associated protein. However, type I pneumocyte differentiation was not affected by Ctgf deletion. Our findings indicate that the absence of Ctgf and/or its protein product, CTGF, may induce pulmonary hypoplasia by both disrupting basic lung developmental processes and restricting thoracic expansion.
authors.affiliation: Department of Anatomy and Neurobiology, Dalhousie University Faculty of Medicine, Halifax, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Baguma-Nibasheka
authors.forename: Boris
authors.initials: B
authors.lastname: Kablar
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D055513:Connective Tissue Growth Factor; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D017874:Immediate-Early Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008168:Lung / Q000002:abnormalities / Q000196:embryology* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission
chemical_list: C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor