Some fine-structural findings on the thyroid gland in Apc (1638T/1638T) mice that express a C-terminus lacking truncated Apc
Some fine-structural findings on the thyroid gland in Apc (1638T/1638T) mice that express a C-terminus lacking truncated Apc
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Apc (1638T/1638T) 小鼠甲状腺的一些精细结构发现，表达缺乏截短的 Apc 的 C 末端
DOI：
10.1007/s00795-011-0553-4
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发表时间：
2012
影响因子：
1.8
通讯作者：
Yokoyama Atsushi
中科院分区：
文献类型：
--
作者：
Shimomura A;Takasaki A;Nomura R;Hayashi N;Senda T;Yokoyama Atsushi
结肠腺瘤性息肉病(APC)是一种多功能蛋白，也是一种肿瘤抑制因子。为了确定APC的C-末端结构域的功能，我们检测了表达缺失C-末端结构域的截短APC的Apc1638T/1638T小鼠。Apc1638T/1638T小鼠无瘤生长，生长迟缓。我们最近报道了Apc1638T/1638T小鼠甲状腺形态和功能的异常，尽管这些异常的机制尚不清楚。在本研究中，我们进一步比较了Apc1638T/1638T和Apc+/+小鼠的甲状腺形态。Apc1638T/1638T小鼠同侧甲状腺左右叶甲状腺滤泡直径有显著差异，而Apc+/+小鼠左右叶甲状腺滤泡直径无明显差异。为了评估甲状腺滤泡细胞的分泌活性，我们对甲状腺滤泡细胞的主要分泌蛋白甲状腺球蛋白和粗面内质网(RER)标记钙网蛋白进行了双重免疫染色。在Apc1638T/1638T滤泡上皮细胞中，甲状腺球蛋白主要与钙网织蛋白共存，而在Apc+/+滤泡上皮细胞中，大量胞浆甲状腺球蛋白与钙网织蛋白不共存。此外，在用促甲状腺激素(TSH)治疗的Apc1638T/1638T小鼠中，电子显微镜分析表明，与Apc+/+小鼠相比，甲状腺滤泡细胞顶端表面的伪足形成频率较低，表明含有碘化甲状腺球蛋白的胶体小滴的再摄取不那么活跃。这些结果提示Apc1638T/1638T小鼠滤泡上皮细胞内甲状腺球蛋白转运和伪足形成存在缺陷，并提示这些细胞的分泌活动受到抑制。
Adenomatous polyposis coli (Apc) is a multifunctional protein as well as a tumor suppressor. To determine the functions of the C-terminal domain of Apc, we examinedApc1638T/1638Tmice that express a truncated Apc lacking the C-terminal domain. TheApc1638T/1638Tmice were tumor free and exhibited growth retardation. We recently reported abnormalities in thyroid morphology and functions ofApc1638T/1638Tmice, although the mechanisms underlying these abnormalities are not known. In the present study, we further compared thyroid gland morphology inApc1638T/1638TandApc+/+mice. The diameters of thyroid follicles in the left and right lobes of the same thyroid gland ofApc1638T/1638Tmice were significantly different whereas theApc+/+mice showed no significant differences in thyroid follicle diameter between these lobes. To assess the secretory activities of thyroid follicular cells, we performed double-immunostaining of thyroglobulin, a major secretory protein of these cells, and the rough endoplasmic reticulum (rER) marker calreticulin. In theApc1638T/1638Tfollicular epithelial cells, thyroglobulin was mostly colocalized with calreticulin whereas in theApc+/+follicular epithelial cells, a significant amount of the cytoplasmic thyroglobulin did not colocalize with calreticulin. In addition, in thyroid-stimulating hormone (TSH)-treatedApc1638T/1638Tmice, electron microscopic analysis indicated less frequent pseudopod formation at the apical surface of the thyroid follicular cells than inApc+/+mice, indicating that reuptake of colloid droplets containing iodized thyroglobulin is less active. These results imply defects in intracellular thyroglobulin transport and in pseudopod formation in the follicular epithelial cells ofApc1638T/1638Tmice and suggest suppressed secretory activities of these cells.