Bone microstructure and its associated genetic variability in 12 inbred mouse strains: microCT study and in silico genome scan.
Bone microstructure and its associated genetic variability in 12 inbred mouse strains: microCT study and in silico genome scan.
复制标题
DOI：
10.1016/j.bone.2007.09.041
复制
发表时间：
2008-02
期刊：
影响因子：
4.1
通讯作者：
Ilya Sabsovich;J. D. Clark;Guochun Liao;G. Peltz;Derek P. Lindsey;Christopher R. Jacobs;W. Yao;T. Guo;W. Kingery
中科院分区：
文献类型：
--
作者：
Ilya Sabsovich;J. D. Clark;Guochun Liao;G. Peltz;Derek P. Lindsey;Christopher R. Jacobs;W. Yao;T. Guo;W. Kingery
对 12 种近交系小鼠的 MicroCT 分析发现了 5 个影响骨骼表型的新染色体区域。不同品系的骨形态以区室和位点特异性方式变化，遗传影响导致了在小梁骨区室中股骨和椎骨中观察到的形态相似性。 简介已知骨骼发育受到遗传和环境因素的调节，但遗传对峰值骨量的影响是否是位点或区室特异性的尚不清楚。本研究检测了12个品系小鼠的皮质骨和骨小梁微结构的遗传变异。 材料和方法采用微CT扫描测量12个品系4个月大近交系雄性小鼠股骨和椎骨的骨小梁和皮质骨形态测量。使用计算基因组作图技术来识别与骨骼特征相关的染色体间隔。结果骨骼微结构在不同菌株之间以区室和位点特异性方式变化。基因组作图确定了 13 个与骨骼特征相关的染色体区间，其中 5 个区间是新的。不同骨位点的小梁微结构在品系之间相关，并且与这些小梁特征相关的大多数染色体间隔在骨骼位点之间共享。相反，股骨中的小梁骨和皮质骨区之间没有共享染色体间隔，尽管这些不同的骨区在不同品系之间存在很强的相关性，这表明环境或内在因素的位点特异性调节。结论总而言之，这些数据证实，在获得峰值骨量时存在定义骨骼表型的不同遗传决定因素，并且骨形态的基因组调节对于骨骼区具有特异性。
MicroCT analysis of 12 inbred strains of mice identified 5 novel chromosomal regions influencing skeletal phenotype. Bone morphology varied in a compartment- and site-specific fashion across strains and genetic influences contributed to the morphometric similarities observed in femoral and vertebral bone within the trabecular bone compartment.INTRODUCTIONSkeletal development is known to be regulated by both heritable and environmental factors, but whether genetic influence on peak bone mass is site- or compartment-specific is unknown. This study examined the genetic variation of cortical and trabecular bone microarchitecture across 12 strains of mice.MATERIALS AND METHODSMicroCT scanning was used to measure trabecular and cortical bone morphometry in the femur and vertebra of 12 strains of 4-month-old inbred male mice. A computational genome mapping technique was used to identify chromosomal intervals associated with skeletal traits.RESULTSSkeletal microarchitecture varied in a compartment- and site-specific fashion across strains. Genome mapping identified 13 chromosomal intervals associated with skeletal traits and 5 of these intervals were novel. Trabecular microarchitecture in different bone sites correlated across strains and most of the chromosomal intervals associated with these trabecular traits were shared between skeletal sites. Conversely, no chromosomal intervals were shared between the trabecular and cortical bone compartments in the femur, even though there was a strong correlation for these different bone compartments across strains, suggesting site-specific regulation by environmental or intrinsic factors.CONCLUSIONIn summary, these data confirm that there are distinct genetic determinants that define the skeletal phenotype at the time when peak bone mass is being acquired, and that genomic regulation of bone morphology is specific for skeletal compartment.