Edderkaoui B, Baylink D J, Beamer W G, Shultz K L, Wergedal J E, Mohan S
Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, 11201 Benton Street, and Department of Biochemistry, Loma Linda University, CA 92357, USA.
Bone. 2007 Sep;41(3):340-5. doi: 10.1016/j.bone.2007.05.013. Epub 2007 Jun 6.
The findings that sex-specific effects on femoral structure and peak bone mineral density (BMD) are linked to quantitative trait loci (QTL) provide evidence for the involvement of specific genes that contribute to gender variation in skeletal phenotype. Based on previous findings that the BMD QTL in chromosome 1 (Chr 1) exerts a sex-specific effect on femoral structure, we predicted that congenic sublines of mice that carry one or more of the Chr 1 BMD loci would exhibit gender difference in the volumetric BMD (vBMD) phenotype. To test this hypothesis, we compared skeletal parameters of male and female of five C57BL/6J (B6).CAST/EiJ (CAST)-1 congenic sublines of mice that carry overlapping CAST chromosomal segments from the vBMD loci in Chr 1. Femur vBMD measurements were performed by the peripheral quantitative computed tomography in male and female mice at 16 weeks of age. The skeletal phenotype of the C175-185 and C178-185 congenic sublines of mice provided evidence for the presence of the BMD1-4 locus at 178-180 Mb from the centromere. This QTL affects femur vBMD only in female mice. In contrast, CAST chromosomal region carrying BMD1-1 locus increased femur vBMD both in male and female mice. Furthermore, a gender specific effect on BMD of femur mid-shaft region (mid-BMD) was identified at 168-176 Mb in Chr 1 (F=16.49, P=0.0002), while no significant effect was found on total femur BMD (F=2.67, P=0.11). Moreover, this study allowed us to locate a body weight QTL at 168-172 Mb of Chr 1, the effect of this locus was altered in female mice that carry CAST chromosomal segment 168-176 Mb of Chr 1. Based on this study, we conclude that Chr 1 carries at least two vBMD gender-dependent loci; one genetic locus at 178-180 Mb (BMD1-4 locus) which affects both mid-shaft and total femur vBMD in female mice only, and another gender-dependent locus at 168-176 Mb (BMD1-2 locus) which affects femur mid-shaft vBMD in female but not male mice.
对股骨结构和峰值骨矿物质密度（BMD）的性别特异性影响与数量性状基因座（QTL）相关，这一发现为特定基因参与骨骼表型的性别差异提供了证据。基于先前的研究结果，即1号染色体（Chr 1）上的BMD QTL对股骨结构具有性别特异性影响，我们预测携带Chr 1上一个或多个BMD基因座的小鼠近交系在体积骨密度（vBMD）表型上会表现出性别差异。为了验证这一假设，我们比较了五个C57BL/6J（B6）.CAST/EiJ（CAST）-1小鼠近交系的雄性和雌性的骨骼参数，这些近交系携带来自Chr 1上vBMD基因座的重叠CAST染色体片段。在16周龄的雄性和雌性小鼠中，通过外周定量计算机断层扫描进行股骨vBMD测量。小鼠C175 - 185和C178 - 185近交系的骨骼表型为在距着丝粒178 - 180 Mb处存在BMD1 - 4基因座提供了证据。这个QTL仅在雌性小鼠中影响股骨vBMD。相反，携带BMD1 - 1基因座的CAST染色体区域在雄性和雌性小鼠中均增加了股骨vBMD。此外，在Chr 1的168 - 176 Mb处发现了对股骨中段区域骨密度（mid - BMD）的性别特异性影响（F = 16.49，P = 0.0002），而对全股骨BMD没有显著影响（F = 2.67，P = 0.11）。此外，这项研究使我们能够在Chr 1的168 - 172 Mb处定位一个体重QTL，该基因座在携带Chr 1的168 - 176 Mb CAST染色体片段的雌性小鼠中的作用发生了改变。基于这项研究，我们得出结论，Chr 1携带至少两个vBMD性别依赖性基因座；一个位于178 - 180 Mb的基因座（BMD1 - 4基因座），仅在雌性小鼠中影响股骨中段和全股骨vBMD，另一个位于168 - 176 Mb的性别依赖性基因座（BMD1 - 2基因座），在雌性而非雄性小鼠中影响股骨中段vBMD。
