Fine mapping of the major bleomycin-induced pulmonary fibrosis susceptibility locus in mice

Mammalian Genome : Official Journal of the International Mammalian Genome Society
Marie-Eve BergeronChristina K Haston

Abstract

Susceptibility to fibrotic lung disease differs among people and among inbred strains of mice exposed to bleomycin where C57BL/6J mice are susceptible and C3H/HeJ mice are spared fibrotic disease. Genetic mapping studies completed in offspring derived from these inbred strains revealed the inheritance of C57BL/6J alleles at loci, including the major locus on chromosome 17, called Blmpf1 bleomycin-induced pulmonary fibrosis 1, to be linked to pulmonary fibrosis in treated mice. In the present study, to reduce the interval of Blmpf1, we bred and phenotyped a panel of subcongenic mice with C3H/HeJ alleles in a C57BL/6J background. Subcongenic mice received bleomycin via osmotic minipump and the fibrosis phenotype was measured histologically. Inheritance of C3H/HeJ alleles from 34.31 to 35.02 Mb was revealed to spare bleomycin-induced pulmonary fibrosis of C57BL/6J mice. From database analysis, 40 protein coding genes have been mapped to this reduced Blmpf1 interval, 18 of which contain C57BL/6J:C3H/HeJ sequence polymorphisms predicted to affect protein structure or to confer allele-dependent expression, and by RT-PCR analysis of lung tissue, we show 6 of these genes to differ in expression between C57BL/6J and C3H/HeJ mice. Genes ...Continue Reading

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Citations

Jun 24, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Evgenia DobrinskikhDavid A Schwartz

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Methods Mentioned

BETA
bronchoalveolar lavage
Assay
lavage
glycosylation
bronchoalveolar

Software Mentioned

GraphPad
Excel
Image Pro Plus
Ensembl

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