Selective breeding as a tool to probe skeletal response to high voluntary locomotor activity in mice.
Selective breeding as a tool to probe skeletal response to high voluntary locomotor activity in mice.
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选择性育种作为探测小鼠骨骼对高自主运动活动反应的工具。
DOI：
10.1093/icb/icn057
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发表时间：
2008
影响因子：
2.6
通讯作者：
GarlandJr,Theodore
中科院分区：
文献类型：
--
作者：
Middleton,KevinM;Kelly,ScottA;GarlandJr,Theodore
我们提出了一种新的小鼠模型的骨骼结构和进化的研究，基于高水平的自愿轮运行的选择性育种。而传统的模型（最初的近交系，最近敲除和转基因）依赖于突变或实验室操作的表型的研究，我们已经研究了骨骼形态的变化，导致许多代的人工选择的高活动的形式，在车轮运行，其中小鼠自愿参与。来自四个重复的High Runner（HR）系的小鼠在暴露于轮（1.12 m周长）的6天的第5天和第6天期间跑几乎三倍的转数。我们发现后肢的骨骼尺寸发生了显著变化，包括方向不对称性降低、股骨头变大和股骨远端变宽。后两者被假设为原始人长距离运动的进化适应。包括有和没有接触轮子的实验组的运动训练研究表明股骨和胫腓骨的直径增加，并表明遗传对可训练性的影响（基因型与环境的相互作用）。对先前发表的后肢骨量数据进行重新分析，发现与使用车轮2个月相关的骨量变化的新模式。在没有接触轮子的情况下，HR小鼠的胫腓骨和脚骨明显较重，而在长期接触轮子的情况下，观察到脚骨质量显著增加，与每日轮子跑步的增加呈线性关系。小鼠表现出最近发现的小肌肉表型（“迷你肌肉”，[MM]由孟德尔隐性基因引起），其中小腿三头肌肌肉复合体的质量比正常个体低约50%，在后肢中具有显著更长和更薄的骨骼。我们提供了出生后1-7周龄小鼠中对照、HR和MM表型的肌肉质量个体发育的新数据。统计学比较显示，除了出生后1周龄外，正常小鼠和MM小鼠之间的小腿三头肌质量和质量校正的小腿三头肌质量均存在高度显著性差异。基于先前观察到的成年MM小鼠中肌球蛋白亚型分布的差异，我们假设肌球蛋白重链IIb型亚型的减少与我们观察到的肌肉质量的个体发育变化有关。
We present a novel mouse-model for the study of skeletal structure and evolution, based on selective breeding for high levels of voluntary wheel running. Whereas traditional models (originally inbred strains, more recently knockouts and transgenics) rely on the study of mutant or laboratory-manipulated phenotypes, we have studied changes in skeletal morphometrics resulting from many generations of artificial selection for high activity in the form of wheel running, in which mice engage voluntarily. Mice from the four replicate High Runner (HR) lines run nearly three times as many revolutions during days 5 and 6 of a 6-day exposure to wheels (1.12 m circumference). We have found significant changes in skeletal dimensions of the hind limbs, including decreased directional asymmetry, larger femoral heads, and wider distal femora. The latter two have been hypothesized as evolutionary adaptations for long-distance locomotion in hominids. Exercise-training studies involving experimental groups with and without access to wheels have shown increased diameters of both femora and tibiafibulae, and suggest genetic effects on trainability (genotype-by-environment interactions). Reanalysis of previously published data on bone masses of hind limbs revealed novel patterns of change in bone mass associated with access to wheels for 2 months. Without access to wheels, HR mice have significantly heavier tibiafibulae and foot bones, whereas with chronic access to wheels, a significant increase in foot bone mass that was linearly related to increases in daily wheel running was observed. Mice exhibiting a recently discovered small-muscle phenotype (“mini-muscle,” [MM] caused by a Mendelian recessive gene), in which the mass of the triceps surae muscle complex is ∼50% lower than in normal individuals, have significantly longer and thinner bones in the hind limb. We present new data for the ontogenetic development of muscle mass in Control, HR, and MM phenotypes in mice of 1–7 weeks postnatal age. Statistical comparisons reveal highly significant differences both in triceps surae mass and mass-corrected triceps surae mass between normal and MM mice at all but the postnatal age of 1 week. Based on previously observed differences in distributions of myosin isoforms in adult MM mice, we hypothesize that a reduction of myosin heavy-chain type-IIb isoforms with accounts for our observed ontogenetic changes in muscle mass.