Genetic dissection of the mouse brain using high-field magnetic resonance microscopy
Genetic dissection of the mouse brain using high-field magnetic resonance microscopy
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DOI：
10.1016/j.neuroimage.2009.01.021
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发表时间：
2009-05-01
期刊：
影响因子：
5.7
通讯作者：
Williams, R. W.
中科院分区：
文献类型：
--
作者：
Badea, A.;Johnson, G. A.;Williams, R. W.
磁共振（MR）成像表明，大脑结构的变化与行为和疾病状态的差异有关。然而，对人类解剖和功能差异之间的因果模型进行前瞻性测试很少是实际可行的。在本研究中，我们将经典小鼠遗传学与高场磁共振相结合，系统地探索和测试了这种跨多个大脑区域的结构-功能关系。我们对2个亲本菌株c57bl /6J (B)和DBA/2J(D)以及9个重组BXD自交系进行了33个区域的分割。所有的菌株都被广泛研究了20多年，使用了一系列的基因、功能、解剖和行为分析。我们按地区和系统比较了菌株内部和不同性别之间的变异水平。全脑平均应变内变异系数（CV）为1.6%；而嗅球、皮层和小脑的变异系数在2.3 - 3.6%之间，而中隔和丘脑外侧核的变异系数高达18%。应变平均值的变化范围从小脑的6.7%，全脑的7.6%，皮质的9.0%，到脑室、丘脑外侧核和脚间核的26%。遗传率平均为0.60±0.18。性别差异并不显著，可能（并且出乎意料）的例外是脑桥（类似于男性大20%）。区域体积的相关矩阵揭示了中枢神经系统功能相关部分之间的高度相关性（例如，边缘系统的组成部分），以及一些在解剖学上没有联系，但可能在功能或基因上耦合的区域之间的高度相关性。(C) 2009爱思唯尔公司版权所有。
Magnetic resonance (MR) imaging has demonstrated that variation in brain structure is associated with differences in behavior and disease state. However, it has rarely been practical to prospectively test causal models that link anatomical and functional differences in humans. In the present study we have combined classical mouse genetics with high-field MR to systematically explore and test such structure-functional relations across multiple brain regions. We segmented 33 regions in two parental strains-C57BL/6J ( B) and DBA/2J(D)-and in nine BXD recombinant inbred strains. All strains have been studied extensively for more than 20 years using a battery of genetic, functional, anatomical, and behavioral assays. We compared levels of variation within and between strains and sexes, by region, and by system. Average within-strain variation had a coefficient of variation ( CV) of 1.6% for the whole brain; while the CV ranged from 2.3 to 3.6% for olfactory bulbs, cortex and cerebellum, and up to similar to 18% for septum and laterodorsal thalamic nucleus. Variation among strain averages ranged from 6.7% for cerebellum, 7.6% for whole brain, 9.0% for cortex, up to similar to 26% for the ventricles, laterodorsal thalamic nucleus, and the interpeduncular nucleus. Heritabilities averaged 0.60 +/- 0.18. Sex differences were not significant with the possible ( and unexpected) exception of the pons (similar to 20% larger in males). A correlation matrix of regional volumes revealed high correlations among functionally related parts of the CNS (e.g., components of the limbic system), and several high correlations between regions that are not anatomically connected, but that may nonetheless be functionally or genetically coupled. (C) 2009 Elsevier Inc. All rights reserved.