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Mapping Susceptibility Genes for the Induction of Pulmonary Fibrosis in Mice* FREE TO VIEW

Richard K. Barth, PhD; LeRoy A. Hanchett, PhD; Clare M. Baecher-Allan, PhD
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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@urmc.rochester.edu.



Chest. 2002;121(3_suppl):21S. doi:10.1378/chest.121.3_suppl.21S
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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-α1 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.

Abbreviations: FGF = fibroblast growth factor; QTL = quantitative trait locus; TNF = tumor necrosis factor

Supported by National Heart, Lung, and Blood Institute grant R01-HL58128.


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