Experiment
Several congenic strains were constructed to study the effects of previously identified femoral volumetric bone mineral density (vBMD) QTLs, namely Bmd5, Bmd7, Bmd8, Bmd13, and Bmd16. C3H/HeJ-derived DNA at each QTL interval was introgressed onto a C57BL/6J genetic background for 6-10 generations. Resulting congenics were estimated to be 98.4%-99.9% C57BL/6J by composition. Parental strain C3H/HeJ exhibits stronger femurs, significantly thicker femoral cortices (over 25% thicker), and 19% greater vBMD compared to parental strain C57BL/6J. However, parental strain C57BL/6J exhibits 13% greater I(p) [polar moment of inertia] compared to C3H/HeJ.
Bmd5 is located at 81.6 cM on mouse Chromosome 1. The C3H/HeJ-derived congenic interval containing Bmd5 spans 36.9 cM (D1Mit282) - 106.3 cM (Tgfbm2, formerly D1Mit17) on mouse Chromosome 1. Authors refer to this congenic as B6.C3H-1T. Congenic animals displayed significantly increased body weight compared to C3H/HeJ and C57BL/6J parentals. A sex-dependent effect was observed for femoral cortical thickness. Male congenics displayed a weight-normalized 29% decrease in cortical area and 43% decrease in femoral I(p) compared to C57BL/6J. Femoral strength was greater in female congenics compared to male congenics. The Bmd5 interval is syntenic to human Chromosome 1q21-23.
Bmd7 is located at 57.4 cM on mouse Chromosome 4. The C3H/HeJ-derived congenic interval containing Bmd7 spans 42.5 cM (D4Mit27) - 81 cM (D4Mit42) on mouse Chromosome 4. Authors refer to this congenic as B6.C3H-4T. Congenic animals displayed significantly increased femoral I(p) compared to C57BL/6J and C3H/HeJ. Congenic animals also displayed increased femoral cortical area compared to C57BL/6J. The Bmd7 interval is syntenic to human Chromosome 1p36,which has been linked to femoral neck BMD in humans.
Bmd8 is located at 51 cM on mouse Chromosome 6. The C3H/HeJ-derived congenic interval containing Bmd8 spans 26.3 cM (D6Mit93) - 51 cM (D6Mit150) on mouse Chromosome 6. Authors refer to this congenic asB6.C3H-6T. Female congenic animals exhibit decreased body weight and decreased femoral vBMD compared to C57BL/6J. Congenic animals also display decreased femoral I(p) compared to C57BL/6J and C3H/HeJ. Bmd8 overlaps with another bone trait QTL, Vtbt5 (38cM), and may represent the same locus.
Bmd13 is located at 35 cM on mouse Chromosome 13. The C3H/HeJ-derived congenic interval containing Bmd13 spans 30 cM (D13Mit245) - 35 cM (D13Mit13) on mouse Chromosome 13. Authors refer to this congenic as B6.C3H-13T. Congenic animals did not exhibit significant bone trait differences compared to C57BL/6J or C3H/HeJ. A small sex-dependent difference was observed for decreased cortical vBMD in females.
Bmd16 is located at 24 cM on mouse Chromosome 18. The C3H/HeJ-derived congenic interval containing Bmd16 spans 16 cM (D18Mit120) - 32 cM (D18Mit124) on mouse Chromosome 18. Authors refer to this congenic as B6.C3H-18T. Congenic animals displayed significantly increased body weight compared to C3H/HeJ and C57BL/6J parentals. Male congenics displayed a weight-normalized 17% decrease in cortical area and a 27% decrease in femoral I(p) compared to C57BL/6J.
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