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Status |
Public on Sep 17, 2010 |
Title |
Cystic Fibrosis Pigs Develop Lung Disease and Exhibit Defective Bacterial Eradication at Birth |
Organism |
Sus scrofa |
Experiment type |
Expression profiling by array
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Summary |
Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). However, understanding its pathogenesis has been hindered by lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with targeted CFTR genes. We now report that within months of birth, CF pigs spontaneously develop hallmark features of CF lung disease including airway inflammation, remodeling, mucus accumulation, and infection. Their lungs contained multiple bacterial species, suggesting an equal opportunity host defense defect. In humans, the temporal and/or causal relationships between inflammation and infection have remained uncertain. To investigate these processes, we studied newborn pigs. Their lungs showed no inflammation, but were less often sterile than controls. Moreover, after intrapulmonary bacterial challenge, CF pigs failed to eradicate bacteria as effectively as wild- type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Finding that CF pigs have a bacterial host defense defect within hours of birth provides an exciting opportunity to further investigate pathogenesis and to test therapeutic and preventive strategies before secondary consequences develop.
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Overall design |
Pig model of human CF lung disease
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Contributor(s) |
Stoltz DA, Meyerholz DK, Pezzulo AA, Ramachandran S, Rogan MP, Davis GJ, Hanfland RA, Wohlford-Lenane C, Dohrn CL, Bartlett JA, Nelson GA, Chang EH, Taft PJ, Ludwig PS, Estin M, Hornick EE, Launspach JL, Samuel M, Rokhlina T, Karp PH, Ostedgaard LS, Uc A, Starne TD, Horswill AR, Brogde KA, Prather RS, Richter SS, Shilyansky J, McCray PB, Zabner J, Welsh MJ |
Citation(s) |
20427821, 22763554 |
Submission date |
Mar 25, 2010 |
Last update date |
May 03, 2013 |
Contact name |
Shyam Ramachandran |
E-mail(s) |
shyam-ramachandran@uiowa.edu
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Phone |
3193356933
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Organization name |
Univ of Iowa
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Department |
Pediatrics
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Lab |
McCray Lab
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Street address |
240G EMRB
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City |
Iowa City |
ZIP/Postal code |
52242 |
Country |
USA |
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Platforms (1) |
GPL3533 |
[Porcine] Affymetrix Porcine Genome Array |
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Samples (40)
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GSM526820 |
Trachea Newborn biological rep 4 |
GSM526821 |
Trachea Newborn biological rep 5 |
GSM526822 |
Trachea Newborn biological rep 6 |
GSM526823 |
Trachea Newborn biological rep 7 |
GSM526824 |
Trachea Newborn biological rep 8 |
GSM526825 |
Trachea Newborn biological rep 9 |
GSM526826 |
Trachea Newborn biological rep 10 |
GSM526827 |
Trachea Newborn biological rep 11 |
GSM526828 |
Trachea Newborn biological rep 12 |
GSM526829 |
Bronchus Newborn biological rep 1 |
GSM526830 |
Bronchus Newborn biological rep 2 |
GSM526831 |
Bronchus Newborn biological rep 3 |
GSM526832 |
Bronchus Newborn biological rep 4 |
GSM526833 |
Bronchus Newborn biological rep 5 |
GSM526834 |
Bronchus Newborn biological rep 6 |
GSM526835 |
Bronchus Newborn biological rep 7 |
GSM526836 |
Bronchus Newborn biological rep 8 |
GSM526837 |
Bronchus Newborn biological rep 9 |
GSM526838 |
Bronchus Newborn biological rep 10 |
GSM526839 |
Bronchus Newborn biological rep 11 |
GSM526840 |
Bronchus Newborn biological rep 12 |
GSM526841 |
Bronchus Newborn biological rep 13 |
GSM526842 |
Bronchus Newborn biological rep 14 |
GSM526843 |
Distal Lung Newborn biological rep 1 |
GSM526844 |
Distal Lung Newborn biological rep 2 |
GSM526845 |
Distal Lung Newborn biological rep 3 |
GSM526846 |
Distal Lung Newborn biological rep 4 |
GSM526847 |
Distal Lung Newborn biological rep 5 |
GSM526848 |
Distal Lung Newborn biological rep 6 |
GSM526849 |
Distal Lung Newborn biological rep 7 |
GSM526850 |
Distal Lung Newborn biological rep 8 |
GSM526851 |
Distal Lung Newborn biological rep 9 |
GSM526852 |
Distal Lung Newborn biological rep 10 |
GSM526853 |
Distal Lung Newborn biological rep 11 |
GSM526854 |
Distal Lung Newborn biological rep 12 |
GSM526855 |
Distal Lung Newborn biological rep 13 |
GSM526856 |
Distal Lung Newborn biological rep 14 |
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Relations |
BioProject |
PRJNA126737 |
Supplementary file |
Size |
Download |
File type/resource |
GSE21071_RAW.tar |
90.9 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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