We speculate that additional backcrosses will further magnify interstrain phenotype differences and enhance the probability of identifying major genetic modifiers using standard and novel backcross and intercross genetic mapping tools with proven success in the detection of human disease gene modifiers.(48,50) Bone trait modifiers identified in the G610C OI mouse likely will include Col1a1 or Col1a2 mutation-specific modifiers, some that are generalizable for many OI mutation loci, and others that overlap with genes associated with common forms of osteoporosis. Here, COL1A1 is linked to osteogenesis imperfecta.