Genetic Regulation of Gelsolin in Lung in Mouse Model and its Potential Broad Spectrum of Biological Functions

Abstract

Considerable studies have been done on the potential biological function of gelsolin and its connection to human immune system, diseases and other disorders. The objective of our study was to identify genetic factors that regulate gelsolin in mouse lung and analyze its function immune system using well defined recombinant inbred strains. For this purpose we chose the BXD recombinant inbred (RI) strains derived from progeny of the C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Whole genome gene expression in lung was used for the eQTL mapping. Bioinformatics tools and genotyping data were used for the candidate gene analysis. Gene network and correlation processes were used to assess the association between gelsolin and biological traits. Data indicated that an eQTL on chromosome 9 covering a genomic area between 21Mb and 30Mb is a major play in regulation of the gelsolin expression level. Analysis of genetic elements within this region revealed that Ncapd3 is the most favorite candidate gene. Its expression level is highly associated to that of gelsolin. The expression level of gelsolin between mouse strains with two genotype of SNP (rs13480109) in a regulatory region of the Ncapd3 showed a significant difference. Additional association analysis suggest that gelsolin may has a broad spectrum of biological function. The expression level of gelsolin has very high correlation with genes in a variety of biological function. These highly associated genes are mainly for protein binding. The expression of gelsolin is also correlated to multiple known immune phenotypes. These data contribute significantly to our current knowledge on the biological function of gelsolin.