由深圳華大基因研究院、丹麥奧爾胡斯大學(xué)、深圳華大方舟生物技術(shù)有限公司等單位組成的科研團隊，采用手工克隆技術(shù)，首次將人體生物鐘基因突變體轉(zhuǎn)入到豬體內(nèi),，從而成功獲得生物節(jié)律轉(zhuǎn)基因模型豬。相關(guān)研究成果已在《公共科學(xué)圖書館·綜合》上發(fā)表,。
生物鐘存在于所有生物中,，從綠藻到動植物再到復(fù)雜的人類，都呈現(xiàn)以近24小時為周期的生物節(jié)律現(xiàn)象,。生物鐘能夠使生物體本身的節(jié)律與環(huán)境的節(jié)律同步化,，因此生物鐘可以調(diào)控生物體日常行為的節(jié)律，以及影響機體健康,。
科研人員通過轉(zhuǎn)基因技術(shù)將人體生物鐘的核心分子成分隱花色素基因1（CRY1）突變體轉(zhuǎn)入到豬體細胞基因組上,，然后采用手工克隆技術(shù)，成功獲得23頭攜帶有人類生物鐘CRY1基因突變體的轉(zhuǎn)基因豬,。通過體溫節(jié)律監(jiān)測發(fā)現(xiàn),，轉(zhuǎn)基因模型豬的體溫節(jié)律發(fā)生了明顯的節(jié)律振蕩變化，其生物鐘基因也發(fā)生了明顯的表達節(jié)律改變,。該研究成果對生物節(jié)律的藥物新靶點發(fā)現(xiàn)及臨床前藥效學(xué)評價具有重要的科學(xué)意義和臨床意義,。（生物谷Bioon.com）
生物谷推薦的英文摘要
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.
