Genetic variability in adult bone density among inbred strains of mice
Genetic variability in adult bone density among inbred strains of mice
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DOI：
10.1016/8756-3282(96)00047-6
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发表时间：
1996-05-01
期刊：
影响因子：
4.1
通讯作者：
Baylink, DJ
中科院分区：
文献类型：
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作者：
Beamer, WG;Donahue, LR;Baylink, DJ
超过70%的人类骨密度的变异性归因于遗传因素，这是对双胞胎、遗传性骨疾病家族和罕见遗传性骨疾病个体的研究结果。我们应用了专门针对小骨骼样本进行改良的PDLC XCT 960 M pQCT，分析了11个近交系雌性小鼠（AKR/J、BALB/cByJ、C3 H/HeJ、C57 BL/6 J、C57 L/J、DBA/2 J、NZB/B1 NJ、SM/J、SJL/BmJ、SWR/BmJ和129/J）的骨，以确定峰值骨密度的遗传差异程度。对来自（a）12月龄近交系雌性和（B）4个品系（C3 H/HeJ、DBA/2 J、BALB/cByJ、C57 BL/6 J）的子集在2、4和8个月时的股骨进行pQCT扫描。此外，还从12月龄时来自4个近交系的相同子集的L5-L 6椎骨和近端趾骨获得pQCT扫描。比较骨骼参数之间的近交系显示显着差异，在每个调查的三个网站。股骨和指骨的总密度和皮质骨密度，矿物质和体积方面的菌株之间的差异。只有皮质骨参数之间的显着不同的应变在椎体网站。就应变差异而言，C3 H/HeJ菌株中任何给定骨骼参数的最高值，而C57 BL/6 J的值绝对或统计学上最低。同样，对于骨部位，皮质骨密度显着相关的应变。另一方面，我们发现，股骨，椎骨，或指骨参数与体重相关，即使体重变化86%，这些近交系。在2、4和8月龄时对C3 H/HeJ、DBA/2 J、BALB/cByJ和C57 BL/6 J雌性进行的股骨发育研究显示，在2月龄及其后各品系间的总密度存在差异。成人骨密度峰值通常在4个月时达到，而股骨在此后持续延长4至8个月。我们的结论是：（1）在近交系小鼠中，可以检测到对股骨、椎骨和指骨骨密度的主要遗传效应;（2）在三个测量部位，皮质骨密度具有共同的遗传调控;（3）在股骨内，调控长度和密度的基因是不同的。
More than 70% of the variability in human bone density has been attributed to genetic factors as a result of studies with twins, osteoporotic families, and individuals with rare heritable bone disorders. We have applied the Stratec XCT 960M pQCT, specifically modified for small skeletal specimens, to analyses of bones from 11 inbred strains (AKR/J, BALB/cByJ, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, NZB/B1NJ, SM/J, SJL/BmJ, SWR/BmJ, and 129/J) of female mice to determine the extent of heritable differences in peak bone density. pQCT scans were taken of femurs from (a) 12-month-old inbred strain females and (b) a subset of four strains (C3H/HeJ, DBA/2J, BALB/cByJ, C57BL/6J) at 2, 4, and 8 months. In addition, pQCT scans were also obtained from L5-L6 vertebrae and proximal phalanges from the same subset of four inbred strains at 12 months of age. Comparison of bone parameters among inbred strains revealed significant differences at each of the three sites investigated. Femoral and phalangeal bones differed among strains with respect to total and cortical density, mineral, and volume. Only cortical bone parameters were significantly different among strains at the vertebral site. With respect to strain differences, the highest value for any given bone parameter was found in the C3H/HeJ strain, whereas C57BL/6J values were absolutely, or statistically, the lowest. Similarly, with respect to bone sites, cortical bone density was significantly correlated among strains. On the other hand, we found that none of the femur, vertebral, or phalangeal parameters correlated with body weight, even though body weight varied by 86% among these inbred strains. The developmental studies of femurs conducted at 2, 4, and 8 months of age with C3H/HeJ, DBA/2J, BALB/cByJ, and C57BL/6J females showed differences in total density among strains at 2 months and thereafter. Adult peak bone density was typically achieved by 4 months, whereas femurs continued to lengthen for 4 to 8 months thereafter. We conclude that (1) major genetic effects on femoral, vertebral, and phalangeal bone density are detectable among inbred strains of mice; (2) cortical bone density shares common genetic regulation at the three measured sites; and (3) within the femur, genes that regulate length and density are different.