Genetic background influences the behavioural and molecular consequences of neurokinin-1 receptor knockout
Genetic background influences the behavioural and molecular consequences of neurokinin-1 receptor knockout
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DOI：
10.1111/j.1460-9568.2008.06043.x
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发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Hunt, S. P.
中科院分区：
文献类型：
--
作者：
McCutcheon, J. E.;Fisher, A. S.;Hunt, S. P.
遗传背景影响动物表型，因此与使用遗传操作小鼠的研究特别相关。下丘脑-垂体-肾上腺皮质（HPA）轴活动的菌株差异可能导致某些突变的背景特异性。在这里，我们分析了HPA轴的组件在小鼠缺乏功能性神经激肽-1受体（NK 1-/-）在两个背景：回交C57 BL/6（B6）和混合C57 BL/6 × 129/sv（129 B6）。我们假设HPA轴活性在这些菌株之间会有所不同，从而导致NK 1-/-表型的差异。我们比较了各组之间的血浆皮质酮水平，发现129 B6小鼠与B6小鼠相比，无论基因型如何，应激诱导的皮质酮水平均升高。虽然基础促肾上腺皮质激素释放因子和应激诱导的c-fos mRNA的水平没有差异的基因型之间的任一株，检查海马内的糖皮质激素受体免疫反应性显示，NK 1-/-小鼠的129 B6背景有升高的表达与野生型相比，而在B6株的基因型之间没有差异。类似地，NK 1-/-小鼠的海马神经发生大于129 B6品系野生型，并且在B6背景的基因型之间没有差异。最后，新奇和吗啡诱导的运动进行了评估。在129 B6背景下的NK 1-/-小鼠表现出对新奇事物的过度运动反应，并且对吗啡的运动刺激特性比野生型更敏感。与此相反，在B6小鼠中，没有观察到任何运动行为的基因型之间的差异。总之，我们发现HPA轴活性在菌株之间存在差异，并且NK 1受体突变具有深刻的背景特异性效应。
Genetic background affects animal phenotype and therefore is of particular relevance to studies using genetically manipulated mice. Strain differences in hypothalamic-pituitary-adrenocortical (HPA) axis activity may contribute to background-specificity of some mutations. Here, we analysed components of the HPA axis in mice lacking a functional neurokinin-1 receptor (NK1-/-) on two backgrounds: backcrossed C57BL/6 (B6) and mixed C57BL/6 x 129/sv (129B6). We hypothesized that HPA axis activity would vary between these strains, leading to differences in the NK1-/- phenotype. We compared levels of plasma corticosterone between the groups, and found 129B6 mice exhibited elevated levels of stress-induced corticosterone compared with B6 mice, regardless of genotype. Although the level of basal corticotrophin-releasing factor and stress-induced c-fos mRNAs did not differ between the genotypes of either strain, examination of glucocorticoid receptor immunoreactivity within the hippocampus revealed that NK1-/- mice on the 129B6 background had elevated expression compared with wild-type, whilst there was no difference between genotypes in the B6 strain. Similarly, hippocampal neurogenesis in NK1-/- mice was greater than in wild-type on the 129B6 strain, and did not differ between genotypes on the B6 background. Finally, novelty- and morphine-induced locomotion were assessed. NK1-/- mice on the 129B6 background exhibited hyperlocomotion in response to novelty and greater sensitivity to the locomotor-stimulating properties of morphine than wild-type. In contrast, in B6 mice, no differences were observed between genotypes for either locomotor behaviour. In summary, we find that HPA axis activity differs between the strains and that there are profoundly background-specific effects of the NK1 receptor mutation.