Il12rb2缺失和Stat1基因敲除小鼠群落中与鼠衣原体相关的肺部和泌尿系统疾病及病理变化

Noah Mishkin, Ileana C Miranda, Sebastian E Carrasco, Christopher Cheleuitte-Nieves, Rodolfo Ricart J Arbona, Claire Wingert, Joseph C Sun, Neil S Lipman
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摘要

鼠衣原体(Chlamydia muridarum,Cm)是一种具有重要历史意义的细胞内细菌,最近再次被发现在研究小鼠群中中度流行。大约 80 年前,Cm 首次被报道为小鼠重症肺炎的致病菌,虽然它已被用于沙眼衣原体感染人类的实验模型,但还没有与自然感染相关的临床疾病的进一步报道。我们观察了两个基因工程小鼠(GEM)品系(Il12rb2KO 和 STAT1KO)的临床疾病和病理变化,它们在已知有沙眼衣原体定植和脱落的各种 GEM 品系群中的干扰素-γ 信号传导和 Th1 CD4+ T 细胞反应受损。临床症状包括体质差、姿势驼背和繁殖力低下。组织病理学显示,Cm呈播散性,在肺部、胃肠道和泌尿生殖系统组织中均有病变。用免疫组化法检测 Cm 主要外膜蛋白-1 抗原,并用针对 Cm 株 Nigg 选择区域的靶探针进行原位杂交,证实了 Cm 的存在。在一只小鼠的尿道乳头状瘤中也发现了 Cm。这些病例为将 Cm 排除在研究小鼠群落之外提供了更多支持。
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Chlamydia muridarum Associated Pulmonary and Urogenital Disease and Pathology in a Colony of Enzootically Infected Il12rb2 Deficient and Stat1 Knockout Mice.

Chlamydia muridarum (Cm), an intracellular bacterium of historical importance, was recently rediscovered as moderately prevalent in research mouse colonies. Cm was first reported as a causative agent of severe pneumonia in mice about 80 y ago, and while it has been used experimentally to model Chlamydia trachomatis infection of humans, there have been no further reports of clinical disease associated with natural infection. We observed clinical disease and pathology in 2 genetically engi- neered mouse (GEM) strains, Il12rb2 KO and STAT1 KO, with impaired interferon-γ signaling and Th1 CD4+ T cell responses in a colony of various GEM strains known to be colonized with and shedding Cm. Clinical signs included poor condition, hunched posture, and poor fecundity. Histopathology revealed disseminated Cm with lesions in pulmonary, gastrointestinal, and urogenital tissues. The presence of Cm was confirmed using both immunohistochemistry for Cm major outer membrane protein-1 antigen and in situ hybridization using a target probe directed against select regions of Cm strain Nigg. Cm was also found in association with a urothelial papilloma in one mouse. These cases provide additional support for excluding Cm from research mouse colonies.

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AALAS Journal Updates for Authors. Chlamydia muridarum Causes Persistent Subclinical Infection and Elicits Innate and Adaptive Immune Responses in C57BL/6J, BALB/cJ, and J:ARC(S) Mice Following Exposure to Shedding Mice. The Final Scene. Investigating the Effect of Enterally Administered Capromorelin on Body Weight in Mice (Mus musculus). Comparison of Terminal Elbow Extension between Humans and Baboons (Papio anubis).
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