Fine mapping of quantitative trait loci affecting organ weights by mouse intersubspecific subcongenic strain analysis

The genetic architecture of organ weights is not well understood. In this study, we fine-mapped quantitative trait loci (QTLs) affecting organ weights by characterizing six intersubspecific subcongenic mouse strains with overlapping and non-overlapping genomic regions on chromosome 2 derived from wild Mus musculus castaneus. QTLs for heart, lung, spleen and kidney weights were revealed on a 6.38-Mb genomic region between two microsatellite markers, D2Mit323 and D2Mit472. Effects of the castaneus alleles at the organ weight QTLs were all opposite in direction to a body weight QTL previously mapped to the same genomic region. In addition, new QTLs for lung and kidney weights were revealed on a different 3.57-Mb region between D2Mit205 and D2Mit182. Their effects were dependent on that of another body weight QTL previously mapped to that genomic region. The organ weight QTLs revealed were all duplicated in independent analyses with F2 intercross populations between subcongenic strains carrying these QTLs and their background strain. The findings suggested that organ weights are not exclusively regulated by genetic loci that commonly influence overall body weight and rather that there are loci contributing to the growth of specific organs only.