Behavioural analysis of congenic mouse strains confirms stress-responsive loci on chromosomes 1 and 12
Behavioural analysis of congenic mouse strains confirms stress-responsive loci on chromosomes 1 and 12
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DOI：
10.1007/s10519-008-9206-3
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发表时间：
2008-07-01
影响因子：
2.6
通讯作者：
Murphy, M.
中科院分区：
文献类型：
--
作者：
Jawahar, M. C.;Brodnicki, T. C.;Murphy, M.
动物对压力环境的反应方式与焦虑相关的行为有关。为了开始确定影响焦虑的遗传因素，我们使用一种改进的开放式活动测试(OFA)来研究近交系小鼠品系的应激反应，称为升高的(E)OFA。特别是，两个菌株在eOFA中表现出高(DBA/2J)或低(C57BL/6J)的应激反应。对这两个菌株之间F-2杂交的遗传研究之前发现了染色体(Chr)1和12上的两个区域，与焦虑相关的行为有关。为了确认这些区域包含应激反应的基因座，我们为连接的ChR1和CHR12区域建立了不同的同源小鼠品系。每个同源菌株都含有一个包含C57BL/6J遗传背景上连锁区域的Dba/2j衍生区间：同源区间介于但不包括类似于48.6Mb和类似于chr1上的194.8 Mb，以及类似于36.2Mb和chr12的远端。用eOFA试验分析了DBA/2J、C57BL/6J和同基因小鼠的一系列应激反应表型。两个同基因品系的应激反应表型与低应激C57BL/6J亲本品系相比有显著差异，但DBA/2J衍生的chr12区间在改变亲本C57BL/6J小鼠的行为表型方面具有比DBA/2J衍生的ChR1区间更大的遗传效应。这些结果证实了ChR1和CHR12上存在胁迫反应基因。我们还发现了新的应激相关表型，这有助于比较和区分DBA/2J、C57BL/6J和同源基因小鼠。
The way in which animals respond to stressful environments correlates with anxiety-related behaviour. To begin identifying the genetic factors that influence anxiety, we have studied the stress-responsiveness of inbred mouse strains using a modified form of the open field activity test (OFA), termed the elevated (e) OFA. In particular, two strains show high (DBA/2J) or low (C57BL/6J) stress-responsiveness in the eOFA. Genetic studies of an F-2 intercross between these two strains previously identified two regions, on chromosomes (Chr) 1 and 12, linked to anxiety-related behaviour. To confirm that these regions contain loci for stress-responsiveness, we established separate congenic mouse strains for the linked Chr1 and Chr12 regions. Each congenic strain harbours a DBA/2J-derived interval encompassing the linked region on the C57BL/6J genetic background: the congenic intervals are between, but not including similar to 48.6 Mb and similar to 194.8 Mb on Chr1, and similar to 36.2 Mb and the distal end of Chr12. Cohorts of DBA/2J, C57BL/6J and congenic mice were analysed for a series of stress-responsive phenotypes using the eOFA test. Both congenic strains had significantly different stress-responsive phenotypes compared to the low-stress C57BL/6J parental strain, but the DBA/2J-derived Chr12 interval had a greater genetic effect than the DBA/2J-derived Chr1 interval for changing the behavioral phenotype of the parental C57BL/6J mouse strain. These results confirmed the presence of stress-responsive loci on Chr1 and Chr12. New stress-related phenotypes were also identified, which aided in comparing and differentiating DBA/2J, C57BL/6J and congenic mice.