Quantitative trait locus for seizure susceptibility on mouse chromosome 5 confirmed with reciprocal congenic strains
Quantitative trait locus for seizure susceptibility on mouse chromosome 5 confirmed with reciprocal congenic strains
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DOI：
10.1152/physiolgenomics.00123.2007
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发表时间：
2007-11-14
影响因子：
4.6
通讯作者：
Buono, Russell J.
中科院分区：
文献类型：
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作者：
Ferraro, Thomas N.;Smith, George G.;Buono, Russell J.
多个数量性状基因座（QTL）定位研究，旨在本地化癫痫发作易感基因在C57 BL/6（B6，癫痫发作抗性）和DBA/2（D2，癫痫发作易感）小鼠检测到一个显着的效果，起源于5号染色体。为了确认最大电休克发作阈值（MEST）的染色体5 QTL的存在和细化的位置，B6和D2小鼠之间的相互同源株创建的DNA标记辅助回交育种策略和研究相对于MEST的变化。由标记D5 Mit 75（近端端节）和D5 Mit 403（远端端节）限定的基因组间隔渐渗10代。还研究了由独立实验室产生的一组5号染色体同源菌株。同类系和对照（亲本遗传背景）小鼠之间的MEST比较表明，影响该性状的基因在所有品系中均被捕获。因此，来自具有来自B6遗传背景上的5号染色体的D2等位基因的品系的小鼠与对照同窝小鼠相比表现出显著较低的MEST，而具有D2遗传背景上的B6 5号染色体等位基因的同源小鼠与对照同窝小鼠相比表现出显著较高的MEST。结合所有同源株系的数据，我们得出结论，MEST的5号染色体QTL的潜在基因位于D5 Mit 108（26 cM）和D5 Mit 278（61 cM）之间的区间。从本文所述的主要同源株产生间隔特异性同源株可用于实现染色体5基因的高分辨率定位，该基因导致B6和D2小鼠之间癫痫发作易感性的巨大差异。
Multiple quantitative trait locus (QTL) mapping studies designed to localize seizure susceptibility genes in C57BL/6 (B6, seizure resistant) and DBA/2 (D2, seizure susceptible) mice have detected a significant effect originating from midchromosome 5. To confirm the presence and refine the position of the chromosome 5 QTL for maximal electroshock seizure threshold (MEST), reciprocal congenic strains between B6 and D2 mice were created by a DNA marker-assisted backcross breeding strategy and studied with respect to changes in MEST. A genomic interval delimited by marker D5Mit75 (proximal to the acromere) and D5Mit403 (distal to the acromere) was introgressed for 10 generations. A set of chromosome 5 congenic strains produced by an independent laboratory was also studied. Comparison of MEST between congenic and control (parental genetic background) mice indicates that genes influencing this trait were captured in all strains. Thus, mice from strains having D2 alleles from chromosome 5 on a B6 genetic background exhibit significantly lower MEST compared with control littermates, whereas congenic mice harboring B6 chromosome 5 alleles on a D2 genetic background exhibit significantly higher MEST compared with control littermates. Combining data from all congenic strains, we conclude that the gene(s) underlying the chromosome 5 QTL for MEST resides in the interval between D5Mit108 (26 cM) and D5Mit278 (61 cM). Generation of interval-specific congenic strains from the primary congenic strains described here may be used to achieve high-resolution mapping of the chromosome 5 gene(s) that contributes to the large difference in seizure susceptibility between B6 and D2 mice.