Alcohol trait and transcriptional genomic analysis of C57BL/6 substrains
Alcohol trait and transcriptional genomic analysis of C57BL/6 substrains
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DOI：
10.1111/j.1601-183x.2008.00405.x
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发表时间：
2008-08-01
影响因子：
2.5
通讯作者：
Bergeson, S. E.
中科院分区：
文献类型：
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作者：
Mulligan, M. K.;Ponomarev, I.;Bergeson, S. E.
C57BL/6近交系小鼠已被广泛用作研究模型；然而，广泛的需求导致了几种具有明显不同表型的 B6 亚株的产生。在这项研究中，我们报告了 50 多年前在两个不同的饲养设施中分离的 C57BL/6 小鼠的两个亚系 C57BL/6J (B6J) 和 C57BL/6NCrl (B6C) 在酒精消耗和酒精偏好方面存在显着差异。据估计，这两个亚系的基因组仅存在所有基因位点的 1-2% 差异，这为提取这些亚系之间与可量化行为差异相关的特定表达特征提供了独特的机会。未经酒精处理的 B6C 和 B6J 小鼠的皮质和纹状体、海马体、小脑和腹侧脑区域的表达谱显示，三个染色体上的间隔富含共调节转录物簇，这些间隔在亚系之间显着不同。额外的分析确定了两个基因组区域，其中包含亚株之间假定的拷贝数差异。与 B6C 相比，14 号染色体上的一个此类区域在 B6J 基因组中包含估计 3n 个拷贝数。在此区间内，发现功能未知的基因 D14Ertd449e 与酒精偏好相关，并且在几个近交系谱系中的拷贝数有所不同。 H2afz、Psen1、Wdfy1 和 Clu 也被确定为可能参与影响饮酒的候选基因。
C57BL/6 inbred mice have been widely used as research models; however, widespread demand has led to the creation of several B6 substrains with markedly different phenotypes. In this study, we report that two substrains of C57BL/6 mice, C57BL/6J (B6J) and C57BL/6NCrl (B6C), separated over 50 years ago at two different breeding facilities differ significantly in alcohol consumption and alcohol preference. The genomes of these two substrains are estimated to differ by only 1-2% of all gene loci, providing a unique opportunity to extract particular expression signatures between these substrains that are associated with quantifiable behavioral differences. Expression profiling of the cortex and striatum, hippocampus, cerebellum and the ventral brain region from alcohol-naive B6C and B6J mice showed intervals on three chromosomes that are enriched in clusters of coregulated transcripts significantly divergent between the substrains. Additional analysis identified two genomic regions containing putative copy number differences between the substrains. One such region on chromosome 14 contained an estimated 3n copy number in the B6J genome compared with B6C. Within this interval, a gene of unknown function, D14Ertd449e, was found to be both associated with alcohol preference and vary in copy number across several inbred strain lineages. H2afz, Psen1, Wdfy1 and Clu were also identified as candidate genes that may be involved in influencing alcohol consumption.