Genes and Behavior Department, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany.
J Biol Rhythms. 2011 Oct;26(5):379-89. doi: 10.1177/0748730411415363.
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 β-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.
视交叉上核（SCN）的手术损伤会严重影响昼夜节律计时系统。SCN 消融术的一个并发症是同时切断 SCN 的传入和传出神经。SCN 内分子钟的基因破坏提供了一种互补的、侵入性更小的实验方法。作者报告了一种新型 Cre 重组酶驱动小鼠的产生和功能分析，该小鼠在 SCN 中以高效率引发同源重组。他们将 Cre 重组酶 cDNA 插入到突触结合蛋白 10（Syt10）基因座中，该基因在 SCN 中强烈表达。杂合性 Synaptotagmin10-Cre（Syt10（Cre））小鼠没有明显的昼夜节律运动表型，而纯合动物显示出轻微的光诱导相位延迟减少。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 细胞中存在强烈的 Cre 活性。除了睾丸外，Cre 活性在非神经元组织中检测不到。作者证明，使用 Syt10（Cre）驱动子条件性删除时钟基因 Bmal1 会使动物失去节律性。
