Minipigs have become important biomedical models for human ailments due to similarities in physiology,anatomy 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, amongst others, cancers and metabolic disorders including obesity and type Ⅱ diabetes.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) which” s dysfunction or absence has been linked to the pathogenesis of rhythm disorders.In this study, we generated transgenic Bama-minipigs by handmade-cloning (HMC) featuring expression of the Cys414-Ala antimorphic human Cryptochrome 1 mutant (hCRY1AP).Using pools of transgenic donor fibroblasts, cloning by HMC was utilized to produce reconstructed embryos that were subsequently transferred to surrogate sows.A total of 23 viable piglets were delivered of which all proved healthy and transgenic.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.
CRY1 mutant Minipigs model Circadin rhythm Proinflammatory cytokines
Huan Liu Jing Luan Jun Wang Huanming Yang Nicklas Heine Staunstrup Yutao Du Yong Li Qiang Wei Chunxin Liu Lars Bolund Gabor Vajta Hongwei Dou Wenxian Yang Ying Xu
BGI-Shenzhen, Shenzhen, 518083, China;ShenZhen Engineering Laboratory for Genomics-Assisted Animal B BGI Ark Biotechnology (BAB), Shenzhen, 518083, China;ShenZhen Engineering Laboratory for Genomics-As BGI-Shenzhen, Shenzhen, 518083, China BGI Ark Biotechnology (BAB), Shenzhen, 518083, China;Department of Biomedicine, University of Aarhus BGI-Shenzhen, Shenzhen, 518083, China;BGI Ark Biotechnology (BAB), Shenzhen, 518083, China;ShenZhen BGI-Shenzhen, Shenzhen, 518083, China;Department of Biomedicine, University of Aarhus, Aarhus C, 800