title: Pathophysiologic consequences following inhibition of a CFTR-dependent developmental cascade in the lung.
abstract: BACKGROUND
  Examination of late gestation developmental genes in vivo may be limited by early embryonic lethality and compensatory mechanisms. This problem is particularly apparent in evaluating the developmental role of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in the cystic fibrosis (CF) phenotype. A previously described transient in utero knockout (TIUKO) technology was used to address the developmental role of CFTR in the rat lung.
  
  
  RESULTS
  Rat fetuses transiently treated with antisense cftr in utero developed pathology that replicated aspects of the human CF phenotype. The TIUKO CF rat developed lung fibrosis, chronic inflammation, reactive airway disease, and the CF Antigen (MRP8/14), a marker for CF in human patients, was expressed.
  
  
  CONCLUSIONS
  The transient in utero antisense technology can be used to evaluate genes that exhibit either early lethality or compensating gene phenotypes. In the lung CFTR is part of a developmental cascade for normal secretory cell differentiation. Absence of CFTR results in a constitutive inflammatory process that is involved in some aspects of CF pathophysiology.
authors.affiliation: Louisiana State University Health Sciences Center, Department of Medicine, School of Medicine, New Orleans, LA 70112, USA. ccohen@lsuhsc.edu
authors.forename: J Craig
authors.initials: JC
authors.lastname: Cohen
authors.forename: Janet E
authors.initials: JE
authors.lastname: Larson
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016375:Antisense Elements (Genetics); D040501:Calgranulin A / Q000235:genetics / Q000502:physiology; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000502:physiology*; D004274:DNA, Recombinant; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D018014:Gene Transfer Techniques; D006801:Humans; D008168:Lung / Q000196:embryology* / Q000473:pathology / Q000502:physiology*; D010641:Phenotype; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016375:Antisense Elements (Genetics); D040501:Calgranulin A; D004274:DNA, Recombinant; C026422:cystic fibrosis serum factor; D019005:Cystic Fibrosis Transmembrane Conductance Regulator