Bleomycin-induced pulmonary fibrosis susceptibility genes in AcB/BcA recombinant congenic mice.
Physiol Genomics
; 23(1): 54-61, 2005 Sep 21.
Article
em En
| MEDLINE
| ID: mdl-16179420
ABSTRACT
The genetic basis of susceptibility to pulmonary fibrosis is largely unknown. Initially, in this study, loci regulating the response of bleomycin-induced pulmonary fibrosis were mapped using a set of recombinant congenic strains bred from pulmonary fibrosis-resistant A/J and susceptible C57BL/6J (B6) mice. Linkage was identified (logarithm of the odds score = 4.9) on chromosome 9, and other suggestive loci were detected. The putative loci included alleles from both the B6 and A/J strains as increasing the fibrosis response of congenic mice. Gene expression analysis with microarrays revealed 3,304 genes or expressed sequence tags to be differentially expressed (P < 0.01) in lung tissue between bleomycin-treated B6 and A/J mice, and 246 of these genes mapped to potential susceptibility loci. Pulmonary genes differentially expressed between bleomycin-treated B6 and A/J mice included those of heparin binding and extracellular matrix deposition pathways. A review of available genomic sequences revealed 809 (43% of total) genes in the linkage intervals to have variations predicted to alter the encoded proteins or their regulation, 68 (8.4%) of which were also differentially expressed. Genomic approaches were combined to produce a set of candidate genes that may influence susceptibility to bleomycin-induced pulmonary fibrosis in the A/JB6 mouse model.
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Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
/
Bleomicina
/
Regulação da Expressão Gênica
/
Predisposição Genética para Doença
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article