RGD Reference Report - Tumor necrosis factor-alpha overexpression in lung disease: a single cause behind a complex phenotype. - Rat Genome Database

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Tumor necrosis factor-alpha overexpression in lung disease: a single cause behind a complex phenotype.

Authors: Lundblad, LK  Thompson-Figueroa, J  Leclair, T  Sullivan, MJ  Poynter, ME  Irvin, CG  Bates, JH 
Citation: Lundblad LK, etal., Am J Respir Crit Care Med. 2005 Jun 15;171(12):1363-70. Epub 2005 Apr 1.
RGD ID: 4143415
Pubmed: PMID:15805183   (View Abstract at PubMed)
PMCID: PMC2718479   (View Article at PubMed Central)
DOI: DOI:10.1164/rccm.200410-1349OC   (Journal Full-text)

RATIONALE: Tumor necrosis factor alpha (TNF-alpha) has been implicated as a key cytokine in many inflammatory lung diseases. These effects are currently unclear, because a transgenic mouse overexpressing TNF-alpha in the lung has been shown in separate studies to produce elements of both emphysema and pulmonary fibrosis. OBJECTIVES: We sought to elucidate the phenotypic effects of TNF-alpha overexpression in a mouse model. MEASUREMENTS: We established the phenotype by measuring lung impedance and thoracic gas volume, and using micro-computed tomography and histology. MAIN RESULTS: We found that airways resistance in this mouse was not different to control mice, but that lung tissue dampening, elastance, and hysteresivity were significantly elevated. Major heterogeneous abnormalities of the parenchyma were also apparent in histologic sections and in micro-computed tomography images of the lung. These changes included airspace enlargement, loss of small airspaces, increased collagen, and thickened pleural septa. We also found significant increases in lung and chest cavity volumes in the TNF-alpha-overexpressing mice. CONCLUSIONS: We conclude that TNF-alpha overexpression causes pathologic changes consistent with both emphysema and pulmonary fibrosis combined with a general lung inflammation, and consequently does not model any single human disease. Our study thus confirms the pleiotropic effects of TNF-alpha, which has been implicated in multiple inflammatory disorders, and underscores the necessity of using a wide range of investigative techniques to link gene expression and phenotype in animal models of disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TNFHumanEmphysema  ISOTnf (Mus musculus) RGD 
TnfRatEmphysema  ISOTnf (Mus musculus) RGD 
TnfMouseEmphysema  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
TNF  (tumor necrosis factor)


Additional Information