Synaptotagmin10-Cre, a Driver to Disrupt Clock Genes in the SCN
Synaptotagmin10-Cre, a Driver to Disrupt Clock Genes in the SCN
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DOI：
10.1177/0748730411415363
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发表时间：
2011-10-01
影响因子：
3.5
通讯作者：
Eichele, Gregor
中科院分区：
文献类型：
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作者：
Husse, Jana;Zhou, Xunlei;Eichele, Gregor
视交叉上核(SCN)的外科损伤对昼夜节律系统有深远的影响。SCN消融的一个并发症是伴随着SCN传入和传出的断裂。对SCN中分子发条的遗传破坏提供了一种补充的、侵入性较小的实验方法。作者报道了一种在SCN中高效引起同源重组的新型Cre重组酶驱动鼠的产生和功能分析。他们将Cre重组酶基因插入到Synaptopagmin10(Syt10)基因座，该基因在SCN中强烈表达。杂合突触素10-Cre(Syt10(Cre))小鼠没有明显的昼夜节律运动表型，纯合子小鼠的光诱导相位延迟略有减少。Syt10(Cre)小鼠与β-半乳糖苷酶报告动物的杂交显示，绝大多数SCN细胞中Cre活性很强。除睾丸外，非神经性组织中未检测到Cre活性。作者证明，使用Syt10(Cre)驱动程序有条件地删除时钟基因BMal1会导致动物心律失常。
Surgical lesion of the suprachiasmatic nuclei (SCN) profoundly affects the circadian timing system. A complication of SCN ablations is the concomitant scission of SCN afferents and efferents. Genetic disruption of the molecular clockwork in the SCN provides a complementary, less invasive experimental approach. The authors report the generation and functional analysis of a new Cre recombinase driver mouse that evokes homologous recombination with high efficiency in the SCN. They inserted the Cre recombinase cDNA into the Synaptotagmin10 (Syt10) locus, a gene strongly expressed in the SCN. Heterozygous Synaptotagmin10-Cre (Syt10(Cre)) mice have no obvious circadian locomotor phenotype, and homozygous animals show slightly reduced light-induced phase delays. Crosses of Syt10(Cre) mice with beta-galactosidase reporter animals revealed strong Cre activity in the vast majority of SCN cells. Cre activity is not detected in nonneuronal tissues with the exception of the testis. The authors demonstrate that conditionally deleting the clock gene Bmal1 using the Syt10(Cre) driver renders animals arrhythmic.