Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck. Rattus norvegicus

Femoral neck bone mineral density and structure candidate gene analysis in Fischer 344 (F344) and Lewis (LEW) rats Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Previously, we identified that the region of 4q21-q41 on chromosome (Chr) 4 uniquely harbors multiple femoral neck quantitative trait loci (QTLs) in inbred Fischer 344 (F344) and Lewis (LEW) rats. In this study we identified the candidate genes for femoral neck density and structure by correlating gene expression in the proximal femur with the femoral neck phenotypes linked to the QTLs on Chr 4. Microarray analysis was performed using RNA extracted from proximal femora of 4-week-old rats from F344, LEW and two other strains. A total of 104 genes in the 4q21-q41 region were differentially expressed (p0.50) with different femoral neck phenotypes and prioritized for further analysis. Ingenuity pathway analysis revealed several direct or indirect relationships among the candidate genes related to bone metabolism including pathways related to beta-estradiol, interleukin 6, insulin growth factor 2, androgen receptor and tumor necrosis factor. Keywords: Comparison of gene expression profiles between F344, LEW, COP and DA rats Overall design: Comparison of differentially expressed genes at the chromosome 4 QTL identified in F344 and LEW F2 rats.