Mulligan M K, Ponomarev I, Boehm S L, Owen J A, Levin P S, Berman A E, Blednov Y A, Crabbe J C, Williams R W, Miles M F, Bergeson S E
Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, USA.
Genes Brain Behav. 2008 Aug;7(6):677-89. doi: 10.1111/j.1601-183X.2008.00405.x. Epub 2008 Apr 7.
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-naïve 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.
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个具有明显不同表型的B6亚系的产生。在本研究中，我们报告称，50多年前在两个不同的繁殖设施中分离出的C57BL/6小鼠的两个亚系，即C57BL/6J（B6J）和C57BL/6NCrl（B6C），在酒精消耗量和酒精偏好方面存在显著差异。据估计，这两个亚系的基因组在所有基因座中仅有1%-2%的差异，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。对未接触过酒精的B6C和B6J小鼠的皮质、纹状体、海马体、小脑和腹侧脑区进行表达谱分析，结果显示三条染色体上的区间富集了亚系之间显著不同的共调控转录本簇。进一步分析确定了两个基因组区域，其中包含亚系之间推定的拷贝数差异。与B6C相比，14号染色体上的一个这样的区域在B6J基因组中的拷贝数估计为3n。在这个区间内，发现一个功能未知的基因D14Ertd449e既与酒精偏好相关，又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酒精消耗的候选基因。
