Genetically engineered mouse lines on a C57BL/6J background are widely employed as preclinical models to study neurodegenerative human disorders and brain tumors. However, because of the lack of comprehensive data on the spontaneous background neuropathology of the C57BL/6J strain, discriminating between naturally occurring changes and lesions caused by experimental mutations can be challenging. In this context, this study aims at defining the spectrum and frequency of spontaneous brain changes in a large cohort of C57BL/6J mice and their association with specific biological variables, including age and sex. Brains from 203 experimentally naive and clinically unremarkable C57BL/6J mice were collected and analyzed by means of histopathology and immunohistochemistry. Mice ranged in age from 3 to 110 weeks with 89 females, 111 males, and 3 unknowns. Sixteen different spontaneous lesion categories were described in this cohort. Age-related neurodegenerative and/or neuroinflammatory findings represented the most common pathologic changes and included (1) Hirano-like inclusions in the thalamic neurons, (2) neuroaxonal dystrophy in the medulla oblongata, (3) periodic acid-Schiff-positive granular deposits in the neuropil of the hippocampus, and (4) progressive neuroinflammation characterized by microgliosis and astrogliosis. Neoplastic conditions, developmental abnormalities, and circulatory disorders were rarely observed incidental findings. In conclusion, this study describes spontaneous age-related brain lesions of the C57BL/6J mouse and provides a reference for evaluating and interpreting the neuropathological phenotype in genetically engineered mouse models developed and maintained on this congenic background.

中文翻译：

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C57BL/6J 小鼠自发性脑损伤。

C57BL/6J 背景下的基因工程小鼠品系被广泛用作研究神经退行性人类疾病和脑肿瘤的临床前模型。然而，由于缺乏 C57BL/6J 菌株自发背景神经病理学的综合数据，区分自然发生的变化和实验突变引起的病变可能具有挑战性。在这种情况下，本研究旨在确定一大群 C57BL/6J 小鼠中自发大脑变化的频谱和频率，以及它们与特定生物变量（包括年龄和性别）的关联。收集了 203 只实验性幼稚和临床上不起眼的 C57BL/6J 小鼠的大脑，并通过组织病理学和免疫组织化学进行了分析。小鼠年龄从 3 周到 110 周不等，有 89 只雌性、111 只雄性和 3 只未知。该队列中描述了 16 种不同的自发性病变类别。与年龄相关的神经退行性和/或神经炎症表现是最常见的病理变化，包括 (1) 丘脑神经元中的 Hirano 样包涵体，(2) 延髓中的神经轴索营养不良，(3) 高碘酸希夫阳性颗粒沉积在海马的神经纤维中，以及 (4) 以小胶质细胞增生和星形胶质细胞增生为特征的进行性神经炎症。肿瘤性疾病、发育异常和循环障碍很少是偶然发现的。总之，