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* From the University of Rochester Cancer Center and Department of Microbiology and Immunology, University of Rochester, Rochester, NY.
Correspondence to: Richard K. Barth, PhD, Associate Professor of Oncology in Microbiology and Immunology, University of Rochester Cancer Center, 601 Elmwood Ave, Box 704, Rochester, NY 14642; e-mail: rick_barth{at}urmc.rochester.edu
Pulmonary
fibrosis is a potentially fatal disease that can result from radiation
or chemotherapeutic treatment of malignancy, exposure to certain
irritants, and idiopathic events. Our studies have focused on the
genetic mechanisms underlying this disease through the analysis of
inbred mouse strain variation in susceptibility to fibrosis induction.
We have identified an inbred mouse strain (DBA/2) that is highly
susceptible to bleomycin-induced pulmonary fibrosis and is genetically
very dissimilar to the standard fibrosis-sensitive strain, C57BL/6, but
similar to the standard fibrosis-resistant strain, BALB/c. Analysis of
a set of backcross progeny generated between DBA/2 and BALB/c strains
indicates that susceptibility to development of pulmonary fibrosis is
controlled primarily by a few (two to three) independent genetic loci.
Genetic linkage using quantitative trait locus (QTL) analysis has led
to the chromosomal assignment of two of these susceptibility loci. One
susceptibility gene is located within a subregion of chromosome 6 that
contains a cluster of genes that are members of the tumor necrosis
factor (TNF)-receptor family, including the 55-kd
TNF-
1 receptor. The second susceptibility gene
has been mapped to the telomeric end of chromosome 13, within an
interval encompassing fibroblast growth factor (FGF)-10, a member of
the FGF gene family that is expressed predominantly in the developing
lung. Analysis of allelic variation in these candidate genes is
underway in order to evaluate their utility as genetic markers for
fibrosis susceptibility and to elucidate their possible role in
influencing the disease process.
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Supported by National Heart, Lung, and Blood Institute grant R01-HL58128.
This article has been cited by other articles:
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A.-M. Lemay and C. K. Haston Bleomycin-induced pulmonary fibrosis susceptibility genes in AcB/BcA recombinant congenic mice Physiol Genomics, September 21, 2005; 23(1): 54 - 61. [Abstract] [Full Text] [PDF] |
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