Sinus hypoplasia precedes sinus infection in a porcine model of cystic fibrosis

Autor: Andrea E. Potash, Thomas O. Moninger, Michael J. Welsh, Sarah E. Ernst, David A. Stoltz, David K. Meyerholz, Jessica C. Sieren, Paul B. McCray, Philip H. Karp, Leah R. Reznikov, Nicholas D. Gansemer, Joseph Zabner, Alejandro A. Pezzulo, Eugene H. Chang, Tanner J. Wallen
Rok vydání: 2012
Předmět:
Male
Aging
Pathology
Cystic Fibrosis
Swine
Organogenesis
Cystic Fibrosis Transmembrane Conductance Regulator
Cystic fibrosis
Pathogenesis
Random Allocation
0302 clinical medicine
Reference Values
Paranasal Sinuses
Medicine
030223 otorhinolaryngology
Sinusitis
Sinus (anatomy)
0303 health sciences
biology
Incidence
Biopsy
Needle
Gene Expression Regulation
Developmental
Immunohistochemistry
Hypoplasia
Cystic fibrosis transmembrane conductance regulator
3. Good health
medicine.anatomical_structure
Female
medicine.medical_specialty
Risk Assessment
03 medical and health sciences
Genetic model
otorhinolaryngologic diseases
Animals
Genetic Predisposition to Disease
Allergy/Rhinology
030304 developmental biology
business.industry
animal model
medicine.disease
Sinus development
Disease Models
Animal
Nasal Mucosa
Paranasal sinuses
Animals
Newborn
Otorhinolaryngology
Chronic Disease
Immunology
biology.protein
sinus disease
business
Zdroj: The Laryngoscope
ISSN: 1531-4995
0023-852X
DOI: 10.1002/lary.23392
Popis: Objectives/Hypothesis: Chronic sinusitis is nearly universal in humans with cystic fibrosis (CF) and is accompanied by sinus hypoplasia (small sinuses). However, whether impaired sinus development is a primary feature of loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or a secondary consequence of chronic infection remains unknown. Our objective was to study the early pathogenesis of sinus disease in CF. Study Design: Animal/basic science research. Methods: Sinus development was studied in a porcine CF model. Results: Porcine sinus epithelia expressed CFTR and exhibited transepithelial anion transport. Disruption of the CFTR gene eliminated both. Sinuses of newborn CF pigs were not infected and showed no evidence of inflammation, yet were hypoplastic at birth. Older CF pigs spontaneously developed sinus disease similar to that seen in humans with CF. Conclusions: These results define a role for CFTR in sinus development and suggest the potential of the CF pig as a genetic model of CF-sinus disease in which to test therapeutic strategies to minimize sinus-related CF morbidity.
Databáze: OpenAIRE
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