Short-term selective breeding for high and low prepulse inhibition of the acoustic startle response; pharmacological characterization and QTL mapping in the selected lines.
Short-term selective breeding for high and low prepulse inhibition of the acoustic startle response; pharmacological characterization and QTL mapping in the selected lines.
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DOI：
10.1016/j.pbb.2008.04.004
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发表时间：
2008-10
影响因子：
3.6
通讯作者：
McWeeney, Shannon
中科院分区：
文献类型：
--
作者：
Hitzemann, Robert;Malmanger, Barry;Belknap, John;Darakjian, Priscila;McWeeney, Shannon
在检测与选择表型的遗传相关性状方面，选择性育种比使用近交系组具有几个重要优势。当前研究的目的是选择性地培育声惊吓反应 (ASR) 的前脉冲抑制 (PPI)，从药理学和行为学角度表征所选品系，并使用这些品系进行数量性状基因座 (QTL) 作图。从通过 C57BL/6J、DBA/2J、BALB/cJ 和 LP/J 近交系杂交形成的异质种小鼠开始，并使用短期选择性育种策略，选择高 PPI 和低 PPI 的动物。选择表型是 80 dB 前脉冲音（比背景噪声高 15 dB）。经过五代选择后，高线和低线存在显着差异（78.1±3.1 vs. 45.2±3.9 [抑制百分比]，p<0.00001）。氟哌啶醇和 MK-801 对 PPI 的影响在高线和低线之间没有差异。然而，在测试的最高剂量（10 mg/kg）下，高线比低线对甲基苯丙胺的破坏性 PPI 作用更敏感。这些品系在基础活性或甲基苯丙胺诱导的运动活性变化方面没有差异。使用一组 768 个 SNP 对高线和低线进行基因分型。在 11 号和 16 号染色体上检测到了显着的 QTL（LOD > 10），这些 QTL 与之前检测到的类似。总体而言，目前的研究表明，PPI 的遗传力足以进行短期选择性育种，并且开发的品系可用于表征与 PPI 调节相关的因素。
Selective breeding offers several important advantages over using inbred strain panels in detecting genetically correlated traits to the selection phenotype. The purpose of the current study was to selectively breed for prepulse inhibition (PPI) of the acoustic startle response (ASR), to pharmacologically and behaviorally characterize the selected lines and to use the lines for quantitative trait loci (QTL) mapping. Starting with heterogeneous stock mice formed by crossing the C57BL/6J, DBA/2J, BALB/cJ and LP/J inbred strains and using a short term selective breeding strategy, animals were selected for High and Low PPI. The selection phenotype was the 80 dB prepulse tone (15 dB above the background noise). After five generations of selection, the High and Low lines differed significantly (78.1±3.1 vs. 45.2±3.9 [percent inhibition], p<0.00001). The effects of haloperidol and MK-801 on PPI were not different between the High and Low lines. However, at the highest dose tested (10 mg/kg), the High line was more sensitive than the Low line to the disruptive PPI effects of methamphetamine. The lines did not differ in terms of basal activity or methamphetamine-induced changes in locomotor activity. The High and Low lines were genotyped using a panel of 768 SNPs. Significant QTLs (LOD > 10) were detected on chromosomes 11 and 16 that appeared similar to those detected previously. Overall, the current study illustrates that the heritability of PPI is sufficient for short term selective breeding and that the lines which are developed can be used to characterize the factors associated with the regulation of PPI.
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影响因子：
3.4
作者：
Brody, SA;Conquet, F;Geyer, MA
通讯作者：
Geyer, MA
影响因子：
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作者：
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DOI：
10.1111/j.1530-0277.1989.tb00310.x
发表时间：
1989-04-01
期刊：
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
影响因子：
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作者：
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通讯作者：
PETERSEN, DR
影响因子：
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作者：
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通讯作者：
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影响因子：
2.6
作者：
Demarest, K;Koyner, J;Hitzemann, R
通讯作者：
Hitzemann, R