由深圳华大基因研究院、丹麦奥尔胡斯大学、深圳华大方舟生物技术有限公司等单位组成的科研团队，采用手工克隆技术，首次将人体生物钟基因突变体转入到猪体内，从而成功获得生物节律转基因模型猪。相关研究成果已在《公共科学图书馆·综合》上发表。
生物钟存在于所有生物中，从绿藻到动植物再到复杂的人类，都呈现以近24小时为周期的生物节律现象。生物钟能够使生物体本身的节律与环境的节律同步化，因此生物钟可以调控生物体日常行为的节律，以及影响机体健康。
科研人员通过转基因技术将人体生物钟的核心分子成分隐花色素基因1（CRY1）突变体转入到猪体细胞基因组上，然后采用手工克隆技术，成功获得23头携带有人类生物钟CRY1基因突变体的转基因猪。通过体温节律监测发现，转基因模型猪的体温节律发生了明显的节律振荡变化，其生物钟基因也发生了明显的表达节律改变。该研究成果对生物节律的药物新靶点发现及临床前药效学评价具有重要的科学意义和临床意义。（生物谷Bioon.com）
生物谷推荐的英文摘要
PLoS One doi:10.1371/journal.pone.0076098
Development of Transgenic Minipigs with Expression of Antimorphic Human Cryptochrome 1
Huan Liu equal contributor， Yong Li equal contributor， Qiang Wei equal contributor， Chunxin Liu， Lars Bolund， Gabor Vajta， Hongwei Dou， Wenxian Yang， Ying Xu， Jing Luan， Jun Wang， Huanming Yang， Nicklas Heine Staunstrup mail， Yutao Du mail
Minipigs have become important biomedical models for human ailments due to similarities in organ anatomy， physiology， and circadian rhythms relative to humans. The homeostasis of circadian rhythms in both central and peripheral tissues is pivotal for numerous biological processes. Hence， biological rhythm disorders may contribute to the onset of cancers and metabolic disorders including obesity and type II diabetes， amongst others. A tight regulation of circadian clock effectors ensures a rhythmic expression profile of output genes which， depending on cell type， constitute about 3–20% of the transcribed mammalian genome. Central to this system is the negative regulator protein Cryptochrome 1 (CRY1) of which the dysfunction or absence has been linked to the pathogenesis of rhythm disorders. In this study， we generated transgenic Bama-minipigs featuring expression of the Cys414-Ala antimorphic human Cryptochrome 1 mutant (hCRY1AP). Using transgenic donor fibroblasts as nuclear donors， the method of handmade cloning (HMC) was used to produce reconstructed embryos， subsequently transferred to surrogate sows. A total of 23 viable piglets were delivered. All were transgenic and seemingly healthy. However， two pigs with high transgene expression succumbed during the first two months. Molecular analyzes in epidermal fibroblasts demonstrated disturbances to the expression profile of core circadian clock genes and elevated expression of the proinflammatory cytokines IL-6 and TNF-α， known to be risk factors in cancer and metabolic disorders.
