Behavioral and genetic investigations of low exploratory behavior in Il18r1(-/-) mice: we can't always blame it on the targeted gene.
Behavioral and genetic investigations of low exploratory behavior in Il18r1(-/-) mice: we can't always blame it on the targeted gene.
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DOI：
10.1016/j.bbi.2010.05.002
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Bolivar VJ
中科院分区：
文献类型：
--
作者：
Eisener-Dorman AF;Lawrence DA;Bolivar VJ
基因靶向技术的发展使免疫系统相关敲除小鼠品系的研究能够促进我们对细胞因子及其受体如何相互作用和影响许多身体系统（包括中枢神经系统）的理解。当我们解释这些敲除菌株的表型数据时，一个关键问题是靶基因以外的基因的潜在作用。尽管许多敲除菌株在C57 BL/6（B6）遗传背景上是同源的，但仍有一定量的来自129亚株的遗传物质用于这些菌株的开发。这种遗传物质可能导致表型错误地归因于靶基因。我们最近报道了Il 10 −/−小鼠的低活动行为，这与这种遗传物质有关，而不是靶基因本身。在目前的研究中，我们通过评估Il 18 −/−和Il 18 r1 −/−敲除小鼠的行为，证实了这些早期发现的普遍性。我们在Il 18 r1 −/−小鼠中发现了低活动和高焦虑样行为，而Il 18 −/−小鼠几乎没有表现出焦虑样行为。尽管Il 18 r1 −/−小鼠被认为是同源品系，但我们已经确定了大量129 P2衍生的遗传物质区域，不仅在1号染色体上的消融Il 18 r1两侧，而且在4号、5号、8号、10号和14号染色体上。我们的研究表明，残留的129衍生基因，而不是靶向的Il 18 r1基因，是造成Il 18 r1 −/−小鼠中低水平活性的原因。定位研究是必要的，以确定基因或基因有助于低活性表型。
The development of gene targeting technologies has enabled research with immune system-related knockout mouse strains to advance our understanding of how cytokines and their receptors interact and influence a number of body systems, including the central nervous system. A critical issue when we are interpreting phenotypic data from these knockout strains is the potential role of genes other than the targeted one. Although many of the knockout strains have been made congenic on a C57BL/6 (B6) genetic background, there remains a certain amount of genetic material from the129 substrain that was used in the development of these strains. This genetic material could result in phenotypes incorrectly attributed to the targeted gene. We recently reported low activity behavior in Il10−/− mice that was linked to this genetic material rather than the targeted gene itself. In the current study we confirm the generalizability of those earlier findings, by assessing behavior in Il18−/− and Il18r1−/− knockout mice. We identified low activity and high anxiety-like behaviors in Il18r1−/− mice, whereas Il18−/− mice displayed little anxiety-like behavior. Although Il18r1−/− mice are considered a congenic strain, we have identified substantial regions of 129P2-derived genetic material not only flanking the ablated Il18r1 on Chromosome 1, but also on Chromosomes 4, 5, 8, 10, and 14. Our studies suggest that residual 129-derived gene(s), rather than the targeted Il18r1 gene, is/are responsible for the low level of activity seen in the Il18r1−/− mice. Mapping studies are necessary to identify the gene or genes contributing to the low activity phenotype.
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影响因子：
3.3
作者：
Curran, B;O'Connor, JJ
通讯作者：
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影响因子：
2.5
作者：
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影响因子：
15.1
作者：
Eisener-Dorman, Amy F.;Lawrence, David A.;Bolivar, Valerie J.
通讯作者：
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影响因子：
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作者：
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通讯作者：
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