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A 2-bp insertion(c.6768insCC) in MC1R causes recessive white coat color in Bama miniature pigs

Journal of Genetics and Genomics 2017年第4期44卷 215-217页

作者： Qitao Jia Chunwei Cao Hai Tang Ying Zhang Qiantao Zheng Xiao Wang Rui Zhang Xianlong Wang Ailing Luo Hong Wei Anming Meng Qi Zhou Hongmei Wang Jianguo Zhao state key laboratory of stem cell and reproductive biology institute of zoologychinese academy of sciencesBeijing 100101China university of chinese academy of sciences Beijing 100101China chinese swine mutagenesis consortium china department of laboratory college of basic medicinethird military medical universitychongqing 400038china school of life sciences tsinghua universityBeijing 100084China

Coat color is an important characteristic of various breeds of domestic animal *** in farm animal coat color is of considerable interest for concealment,communication and protection against solar radiation（Slominski et al.,2004）.It also plays an important role in the regulation of physiological processes（Miyagi and Terai,2013）.

关键词： miniature recessive c.67_68insCC insertion physiological mutant originally phenotype spots linkage

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A harlequin ichthyosis pig model with a novel ABCA12 mutation can be rescued by acitretin treatment

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Journal of Molecular Cell Biology 2019年第12期11卷 1029-1041页

作者： Xiao Wang Chunwei Cao Yongshun Li Tang Hai Qitao Jia Ying Zhang Qiantao Zheng Jing Yao Guosong Qin Hongyong Zhang Ruigao Song Yanfang Wang Guanghou Shui Sin Man Lam Zhonghua Liu Hong Wei Anming Meng Qi Zhou Jianguo Zhao State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of chinese Academy of Sciences Beijing 100049China State Key Laboratory of Animal Nutrition Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100081China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China College of Life Science Northeast Agricultural University of ChinaHarbin 150030China Department of Laboratory Animal Science College of Basic Medical SciencesThird Military Medical UniversityChongqing 400038China School of Life Sciences Tsinghua UniversityBeijing 100084China chinese swine mutagenesis consortium Beijing 100101China

Harlequin ichthyosis (HI) is a severe genetic skin disorder and caused by mutation in the ATP-binding cassette A12 (ABCA12) gene. The retinoid administration has dramatically improved long-term survival of HI, but improvements are still needed. However, the ABCA12 null mice failed to respond to retinoid treatment, which impedes the development of novel cure strategies for HI. Here we generated an ethylnitrosourea mutagenic HI pig model (named Z9), which carries a novel deep intronic mutation IVS49-727 A>G in the ABCA12 gene, resulting in abnormal mRNA splicing and truncated protein production. Z9 pigs exhibit significant clinical symptom as human patients with HI. Most importantly, systemic retinoid treatment significantly prolonged the life span of the mutant pigs via improving epidermal maturation, decreasing epidermal apoptosis, and triggering the expression of ABCA6. Taken together, this pig model perfectly resembles the clinical symptom and molecular pathology of patients with HI and will be useful for understanding mechanistic insight and developing therapeutic strategies.

关键词： harlequin ichthyosis ABCA12 pig model acitretin ENU mutagenesis deep intronic mutation

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Human apo-SRP72 and SRP68/72 complex structures reveal the molecular basis of protein translocation

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Journal of Molecular Cell Biology 2017年第3期9卷 220-230页

作者： Yina Gao Qi Zhang Yue Lang Yang Liu Xiaofei Dong Zhenhang Chen Wenli Tian Jun Tang Wei Wu Yufeng Tong Zhongzhou Chen Beijing Advanced Innovation Center for Food Nutrition and Human Health State Key Laboratory of Agrobiotechno[ogy China Agricultural University Beijing 3.00193 China Structural Genomics consortium Toronto Ontario M5G 1L7 Canada College of Veterinary Medicine China Agricultural University Beijing 100193 China Institute of Apicultural Research Chinese Academy of Agricultural Sciences Beijing 100093 China Department of Pharmacotogy and Toxicology Universityof Toronto Toronto Ontario M5G 1L7 Canada

The co-translational targeting or insertion of secretory and membrane proteins into the endoplasmic reticulum （ER） is a key biological process mediated by the signal recognition particle （SRP）. In eukaryotes, the SRP68-SRP72 （SRP68/72） heterodimer plays an essen- tial role in protein translocation. However, structural information on the two largest SRP proteins, SRP68 and SRP72, is limited, espe- cially regarding their interaction. Herein, we report the first crystal structures of human apo-SRP72 and the SRP68/72 complex at 2.91A. and 1.7A resolution, respectively. The SRP68-binding domain of SRP72 contains four atypical tetratricopeptide repeats （TPR） and a flexible C-terminal cap. Apo-SRP72 exists mainly as dimers in solution. To bind to SRP68, the SRP72 homodimer disassociates, and the indispensable C-terminal cap undergoes a pronounced conformational change to assist formation of the SRP68/72 heterodi- mer. A 23-residue polypeptide of SRP68 is sufficient for tight binding to SRP72 through its unusually hydrophobic and extended sur- face. Structural, biophysical, and mutagenesis analyses revealed that cancer-associated mutations disrupt the SRP68-SRP72 interaction and their co-localization with ER in mammalian cells. The results highlight the essential role of the SRP68-SRP72 inter- action in SRP-mediated protein translocation and provide a structural basis for disease diagnosis, pathophysiology, and drug design.

关键词： SRP72 SRP68 protein translocation crystal structures cancer protein-protein interaction signal recognition particle

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A review of the resistome within the digestive tract of livestock

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Journal of Animal Science and Biotechnology 2022年第3期13卷 642-661页

作者： Tao Ma Tim A.McAllister Le Luo Guan Key laboratory of Feed Biotechnology of the Ministry of Agriculture Institute of Feed ResearchChinese Academy of Agricultural SciencesBeijing 100081China Department of Agricultural Food and Nutritional ScienceUniversity of AlbertaT6G2P5EdmontonABCanada Lethbridge Research and Development Centre LethbridgeAB T1J 4P4Canada

Antimicrobials have been widely used to prevent and treat infectious diseases and promote growth in food-production ***,the occurrence of antimicrobial resistance poses a huge threat to public and animal health,especial y in less developed countries where food-producing animals often intermingle with *** limit the spread of antimicrobial resistance from food-production animals to humans and the environment,it is essential to have a comprehensive knowledge of the role of the resistome in antimicrobial resistance(AMR),The resistome refers to the col ection of al antimicrobial resistance genes associated with microbiota in a given *** dense microbiota in the digestive tract is known to harbour one of the most diverse resistomes in *** of the resistome in the digestive tract of humans and animals are increasing exponential y as a result of advancements in next-generation sequencing and the expansion of bioinformatic resources/tools to identify and describe the *** this review,we outline the various tools/bioinformatic pipelines currently available to characterize and understand the nature of the intestinal resistome of swine,poultry,and *** then propose future research directions including analysis of resistome using long-read sequencing,investigation in the role of mobile genetic elements in the expression,function and transmission of *** review outlines the current knowledge and approaches to studying the resistome in food-producing animals and sheds light on future strategies to reduce antimicrobial usage and control the spread of AMR both within and from livestock production systems.

关键词： Antimicrobial resistance Antimicrobial resistance gene Digestive tract Food-producing animal Metagenomic sequencing Resistome

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