Genetic linkage analysis of pulmonary fibrotic response to silica in mice

¹ Dept of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, 960-1295 Japan

^* To whom correspondence should be addressed. E-mail: yohtsuka{at}kvf.biglobe.ne.jp.

	Abstract

Inter-individual variations in the development of silicosis even in the same environments have been reported, which suggest the contribution of genetic factors in its etiology.

Is there significant genetic influence on the development of silicosis? Which genetic loci are responsible for the response?

Eight strains of inbred mice were used to examine the genetic influence on the lung fibrotic response to silica exposure. After breeding intercross between the most susceptible strain and the resistant one, a genome-wide linkage analysis of quantitative trait loci (QTLs) was performed. Hydroxyproline was applied as an index, and genotypes of 167 marker genes were analyzed by the fragment analysis using a capillary-type sequencer.

There was significant inter-strain difference among 8 strains of mice on the mean concentration of hydroxyproline contents. Breeding studies were proceeded between the most susceptible strain C57BL/6J and the most resistant CBA/J. A genome-wide linkage analysis of silica-exposed intercross cohort identified significant QTLs on chromosome 4 and suggestive QTLs on chromosomes 3 and 18 respectively.

Genetic factors play significant roles in lung fibrotic responses to silica and we found one significant QTL and 2 suggestive QTLs.

This article has been cited by other articles:

				D. R. Prows, A. V. Winterberg, W. J. Gibbons Jr., B. B. Burzynski, C. Liu, and T. G. Nick Reciprocal backcross mice confirm major loci linked to hyperoxic acute lung injury survival time Physiol Genomics, July 9, 2009; 38(2): 158 - 168. [Abstract] [Full Text] [PDF]

				B. B. Moore and C. M. Hogaboam Murine models of pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L152 - L160. [Abstract] [Full Text] [PDF]