Paulsen J E, Namork E, Steffensen I L, Eide T J, Alexander J
Dept. of Environmental Medicine, National Institute of Public Health, and National Hospital, Oslo, Norway.
Scand J Gastroenterol. 2000 May;35(5):534-9. doi: 10.1080/003655200750023813.
Min mice are heterozygous for a nonsense mutation in the murine adenomatous polyposis coli (APC) gene and spontaneously develop multiple intestinal neoplasms similar to the familial adenomatous polyposis (FAP) syndrome in humans. Aberrant crypt foci (ACF) are assumed to be preneoplastic lesions in both murine and human colon carcinogenesis and have been observed in FAP patients. Light microscopic examination of the colonic mucosa of 42 Min mice did not show even a single 'classical' ACF on the basis of previously defined criteria, specifying that they are elevated above the surrounding mucosa. However, in Min mice we discovered aberrant crypt foci of a different type, which we denoted ACF(Min). In contrast to the classical type, ACF(Min) were not elevated above the surrounding mucosa, their detection was totally dependent on methylene blue staining and transillumination, and they could not be identified with scanning electron microscopy. Histopathologic examination of ACF(Min) showed dysplastic crypts, similar to those found in larger lesions--that is, microadenomas in the Min mouse. The number of ACF(Min) increased up to the age of 6 weeks and then seemed to remain at a constant level of approximately four per colon. In conclusion, by transillumination of whole-mount preparations stained with methylene blue, we have identified and quantified small microscopic lesions that may be precursors of colonic adenomas in Min mice.
Min小鼠在鼠源腺瘤性结肠息肉病（APC）基因中存在一个无义突变的杂合子，会自发形成多个肠道肿瘤，类似于人类的家族性腺瘤性息肉病（FAP）综合征。异常隐窝灶（ACF）被认为是小鼠和人类结肠癌发生过程中的癌前病变，在FAP患者中也有观察到。根据先前定义的标准，即ACF高于周围黏膜，对42只Min小鼠的结肠黏膜进行光学显微镜检查，甚至未发现一个“典型”的ACF。然而，在Min小鼠中，我们发现了一种不同类型的异常隐窝灶，我们将其命名为ACF(Min)。与经典类型不同，ACF(Min)并不高于周围黏膜，其检测完全依赖于亚甲蓝染色和透照，并且无法通过扫描电子显微镜识别。ACF(Min)的组织病理学检查显示出发育异常的隐窝，类似于在较大病变中发现的隐窝，即Min小鼠中的微腺瘤。ACF(Min)的数量在6周龄前增加，然后似乎保持在每只结肠约4个的恒定水平。总之，通过对用亚甲蓝染色的整装标本进行透照，我们识别并量化了可能是Min小鼠结肠腺瘤前体的微小微观病变。
