Doxycycline-Induced Expression of Transgenic Human Tumor Necrosis Factor α in Adult Mice Results in Psoriasis-like Arthritis
Doxycycline-Induced Expression of Transgenic Human Tumor Necrosis Factor α in Adult Mice Results in Psoriasis-like Arthritis
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强力霉素诱导成年小鼠转基因人类肿瘤坏死因子α的表达导致银屑病样关节炎
DOI：
10.1002/art.38026
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发表时间：
2013
影响因子：
--
通讯作者：
Wixler V
中科院分区：
文献类型：
--
作者：
Retser E;Schied T;Skryabin B;Vogl T;Kanczler J;Hamann N;Niehoff A;Hermann S;Eisenblätter M;Wachsmuth L;van Lent P;Loser K;Roth J;Zaucke F;Ludwig S;Wixler V
目的建立强力霉素诱导的人肿瘤坏死因子α（TNFα）转基因小鼠，以克服现有TNFα组成型表达转基因小鼠的主要缺点，这是将它们与各种基因敲除或转基因小鼠杂交的限制。方法产生了在多西环素给药后仅表达人TNFα细胞因子的转基因小鼠系，并分析了疾病的发作。转基因小鼠出现了炎性关节炎和银屑病样表型，前爪和后爪受到显著影响。观察到“香肠指”的形成，并观察到远端指间关节和指甲畸形的特征性受累。滑膜增生、附着点炎、软骨和骨改变、血管翳组织的形成以及皮肤表皮和指甲基质的炎症早在用多西环素治疗小鼠后1周就出现，并且随着时间的推移而加重。在开始刺激后6周，通过去除强力霉素消除人TNFα表达导致最先进的宏观和组织学疾病的快速解决，3-6周后，只有最小的疾病体征是visible.ConclusionUpon强力霉素给药，强力霉素诱导的人TNFα转基因小鼠显示炎性关节炎的主要特征。它代表了研究关节炎分子机制的独特动物模型，特别是疾病发生的早期阶段和TNFα表达消除后的组织重塑步骤。此外，多西环素诱导的人TNFα转基因小鼠与各种敲除或转基因小鼠的无限制杂交为阐明与TNFα协同作用的各种信号分子的作用开辟了新的可能性。
ObjectiveTo generate doxycycline‐inducible human tumor necrosis factor α (TNFα)–transgenic mice to overcome a major disadvantage of existing transgenic mice with constitutive expression of TNFα, which is the limitation in crossing them with various knockout or transgenic mice.MethodsA transgenic mouse line that expresses the human TNFα cytokine exclusively after doxycycline administration was generated and analyzed for the onset of diseases.ResultsDoxycycline‐inducible human TNFα–transgenic mice developed an inflammatory arthritis– and psoriasis‐like phenotype, with fore and hind paws being prominently affected. The formation of “sausage digits” with characteristic involvement of the distal interphalangeal joints and nail malformation was observed. Synovial hyperplasia, enthesitis, cartilage and bone alterations, formation of pannus tissue, and inflammation of the skin epidermis and nail matrix appeared as early as 1 week after the treatment of mice with doxycycline and became aggravated over time. The abrogation of human TNFα expression by the removal of doxycycline 6 weeks after beginning stimulation resulted in fast resolution of the most advanced macroscopic and histologic disorders, and 3–6 weeks later, only minimal signs of disease were visible.ConclusionUpon doxycycline administration, the doxycycline‐inducible human TNFα–transgenic mouse displays the major features of inflammatory arthritis. It represents a unique animal model for studying the molecular mechanisms of arthritis, especially the early phases of disease genesis and tissue remodeling steps upon abrogation of TNFα expression. Furthermore, unlimited crossing of doxycycline‐inducible human TNFα–transgenic mice with various knockout or transgenic mice opens new possibilities for unraveling the role of various signaling molecules acting in concert with TNFα.
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Htnfalpha转基因小鼠的广泛表型表征。
影响因子：
--
作者：
Hayward, Michael D;Jones, Beverly K;Saparov, Arman;Hain, Heather S;Trillat, Anne-Cecile;Bunzel, Michelle M;Corona, Aaron;Li-Wang, Bifang;Strenkowski, Bryan;Giordano, Caroline;Shen, Hai;Arcamone, Emily;Weidlick, Jeffrey;Vilensky, Maria;Tugusheva, Marina;Felkner, Roland H;Campbell, William;Rao, Yu;Grass, David S;Buiakova, Olesia
通讯作者：
Buiakova, Olesia
影响因子：
27.4
作者：
Korb-Pap, Adelheid;Stratis, Athanasios;Redlich, Kurt
通讯作者：
Redlich, Kurt
影响因子：
10
作者：
通讯作者：
--
影响因子：
--
作者：
van Lent, Peter L. E. M.;Blom, Arjen B.;van den Berg, Wim B.
通讯作者：
van den Berg, Wim B.
影响因子：
7
作者：
Pei, Yong;Harvey, Anita;Thirunavukkarasu, Kannan
通讯作者：
Thirunavukkarasu, Kannan