First Author | Lemay AM | Year | 2005 |
Journal | Physiol Genomics | Volume | 23 |
Issue | 1 | Pages | 54-61 |
PubMed ID | 16179420 | Mgi Jnum | J:101567 |
Mgi Id | MGI:3604270 | Doi | 10.1152/physiolgenomics.00095.2005 |
Citation | Lemay AM, et al. (2005) Bleomycin-induced pulmonary fibrosis susceptibility genes in AcB/BcA recombinant congenic mice. Physiol Genomics 23(1):54-61 |
abstractText | 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/J:B6 mouse model. |