Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and The Rockefeller University, New York, New York;, Email:
Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and The Rockefeller University, New York, New York; Center of Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, New York.
Comp Med. 2022 Aug 1;72(4):230-242. doi: 10.30802/AALAS-CM-22-000045. Epub 2022 Jul 8.
(Cm) was detected in 2 colonies of mice with lymphoplasmacytic pulmonary infiltrates by using PCR and immunohistochemistry. This discovery was unexpected, as Cm infection had not been reported in laboratory mice since the 1940s. A Cm specific PCR assay was developed and testing implemented for the resident colonies of 8 vivaria from 3 academic institutions, 58 incoming mouse shipments from 39 academic institutions, and mice received from 55 commercial breeding colonies (4 vendors). To estimate Cm's global prevalence in research colonies, a database containing 11,387 metagenomic fecal microbiota samples from 120 institutions and a cohort of 900 diagnostic samples from 96 institutions were examined. Results indicate significant prevalence among academic institutions, with Cm detected in 63% of soiled bedding sentinels from 3 institutions; 33% of incoming mouse shipments from 39 academic institutions; 14% of 120 institutions submitting microbiota samples; and 16% of the diagnostic sample cohort. All samples from commercial breeding colonies were negative. In addition, naïve NOD. Cg-Il2rg/SzJ (NSG) mice exposed to Cm-shedding mice and/or their soiled bedding developed clinical disease at 21 to 28 d after exposure. These mice had a moderate-to-severe histiocytic and neutro- philic bronchointerstitial pneumonia, with their respiratory epithelium demonstrating inclusions, chlamydial major outer membrane protein immunostaining, and hybridization with a Cm reference sequence (GenBank accession no. U68436). Cm was isolated from lungs, cecum, and feces of a Cm-infected NSG mouse by using HeLa 229 cells. The considerable prevalence of Cm is likely due to widespread global interinstitutional distribution of unique mouse strains and failure to recognize that some of these mice were from enzootically infected colonies. Given that experimental Cm colonization of mice results in a robust immune response and, on occasion, pathology, natural infection may confound experimental results. Therefore, Cm should be excluded and eradicated from enzootically infected mouse colonies.
（Cm）通过 PCR 和免疫组织化学在 2 株具有淋巴浆细胞性肺浸润的小鼠中被检测到。这一发现出乎意料，因为自 20 世纪 40 年代以来，实验室小鼠中就没有报道过 Cm 感染。开发了一种 Cm 特异性 PCR 检测方法，并对来自 3 个学术机构的 8 个隔离区的常驻种群、来自 39 个学术机构的 58 批新引进的小鼠以及来自 55 个商业繁殖群（4 个供应商）的小鼠进行了检测。为了估计 Cm 在研究群体中的全球流行率，对来自 120 个机构的包含 11387 个宏基因组粪便微生物组样本的数据库和来自 96 个机构的 900 个诊断样本的队列进行了检查。结果表明，学术机构中存在显著的流行率，来自 3 个机构的污染垫哨兵中有 63%检测到 Cm；来自 39 个学术机构的 58 批新引进的小鼠中有 33%检测到 Cm；120 个提交微生物组样本的机构中有 14%检测到 Cm；96 个诊断样本队列中有 16%检测到 Cm。所有商业繁殖群的样本均为阴性。此外，暴露于排菌小鼠及其污染垫的初始 NOD.Cg-Il2rg/SzJ（NSG）小鼠在暴露后 21 至 28 天发展为临床疾病。这些小鼠患有中度至重度组织细胞性和中性粒细胞性支气管间质性肺炎，其呼吸道上皮有包涵体、衣原体主要外膜蛋白免疫染色和与 Cm 参考序列（GenBank 登录号 U68436）杂交。通过使用 HeLa 229 细胞从感染 Cm 的 NSG 小鼠的肺部、盲肠和粪便中分离出 Cm。Cm 的广泛流行很可能是由于独特的小鼠品系在全球范围内广泛分布于不同机构，并且没有认识到其中一些小鼠来自地方性感染的群体。鉴于实验性 Cm 定植于小鼠会引起强烈的免疫反应，并且有时会导致病理变化，因此自然感染可能会使实验结果复杂化。因此，应从地方性感染的小鼠群体中消除 Cm。
