Circadian rhythms persist in almost all organisms and are crucial for maintaining appropriate timing in physiology and behaviour. Here, we describe a mouse mutant where the central mammalian pacemaker, the suprachiasmatic nucleus (SCN), has been genetically ablated by conditional deletion of the transcription factor Zfhx3 in the developing hypothalamus. Mutants were arrhythmic over the light-dark cycle and in constant darkness. Moreover, rhythms of metabolic parameters were ablated in vivo although molecular oscillations in the liver maintained some rhythmicity. Despite disruptions to SCN cell identity and circuitry, mutants could still anticipate food availability, yet other zeitgebers - including social cues from cage-mates - were ineffective in restoring rhythmicity although activity levels in mutants were altered. This work highlights a critical role for Zfhx3 in the development of a functional SCN, while its genetic ablation further defines the contribution of SCN circuitry in orchestrating physiological and behavioral responses to environmental signals.

昼夜节律几乎存在于所有生物体中，对于维持生理和行为的适当时间至关重要。在这里，我们描述了一种小鼠突变体，其中中央哺乳动物起搏器视交叉上核 (SCN) 已通过条件性删除发育中的下丘脑中的转录因子Zfhx3进行基因消融。突变体在明暗循环和持续黑暗中心律失常。此外，代谢参数的节律在体内被消除尽管肝脏中的分子振荡保持了一定的节律性。尽管 SCN 细胞身份和电路受到破坏，但突变体仍然可以预测食物的可用性，但其他时代——包括来自笼中伴侣的社会线索——在恢复节律性方面无效，尽管突变体的活动水平发生了变化。这项工作突出了Zfhx3在功能性 SCN 发展中的关键作用，而其基因消融进一步定义了 SCN 电路在协调对环境信号的生理和行为反应方面的贡献。