Ponder Christine A, Munoz Michaelanne, Gilliam T Conrad, Palmer Abraham A
Department of Genetics and Development, Columbia University, New York, New York, USA.
Mamm Genome. 2007 Apr;18(4):221-8. doi: 10.1007/s00335-007-9013-9. Epub 2007 May 10.
We measured fear conditioning (FC) in a panel of chromosome substitution strains (CSS) created using the C57BL/6J (B6) and A/J (AJ) inbred strains. Mice were trained to associate a specific context and tone with a foot shock. FC was measured by observing freezing behavior during re-exposure to the context and tone. Freezing to context was more than twofold greater in the AJ strain relative to the B6 strain. Among the CSS we identified four strains with higher (CSS-6, -10, -11, and -18) and two strains with lower (CSS-7 and -14) freezing to context. CSS-10 and -18 also showed higher freezing to tone, while CSS-12 showed less freezing to tone. CSS-1 has been implicated in open-field (OF) and light-dark box (LDB); we observed significant activity differences prior to training but no differences in FC. Chromosomes 6 and 10 have been associated with differences in anxiety-like behaviors, suggesting the existence of pleiotropic alleles that influence both learned and innate fear. By utilizing a genetic reference population, we have identified chromosomes that pleiotropically influence multiple phenotypes hypothesized to reflect a common ethologic construct that has been termed emotionality. The CSS provide a straightforward means of isolating the underlying genetic factors.
我们在一组使用C57BL/6J(B6)和A/J(AJ)近交系培育的染色体代换系(CSS)中测量了恐惧条件反射(FC)。训练小鼠将特定的环境和音调与足部电击联系起来。通过观察再次暴露于该环境和音调时的僵住行为来测量FC。相对于B6品系,AJ品系中对环境的僵住反应高出两倍多。在CSS中,我们鉴定出四个对环境僵住反应较高的品系(CSS-6、-10、-11和-18)以及两个对环境僵住反应较低的品系(CSS-7和-14)。CSS-10和-18对音调的僵住反应也较高,而CSS-12对音调的僵住反应较少。CSS-1与旷场试验(OF)和明暗箱试验(LDB)有关;我们在训练前观察到显著的活动差异,但在FC方面没有差异。6号和10号染色体与焦虑样行为的差异有关,这表明存在影响学习性恐惧和先天性恐惧的多效性等位基因。通过利用一个遗传参考群体,我们已经鉴定出对多种表型具有多效性影响的染色体,这些表型被假设反映了一种被称为情绪性的共同行为学结构。CSS提供了一种直接分离潜在遗传因素的方法。