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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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 examined Apc 1638T/1638T mice that express a truncated Apc lacking the C-terminal domain. The Apc 1638T/1638T mice were tumor free and exhibited growth retardation. We recently reported abnormalities in thyroid morphology and functions of Apc 1638T/1638T mice, although the mechanisms underlying these abnormalities are not known. In the present study, we further compared thyroid gland morphology in Apc 1638T/1638T and Apc +/+ mice. The diameters of thyroid follicles in the left and right lobes of the same thyroid gland of Apc 1638T/1638T mice were significantly different whereas the Apc +/+ 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 the Apc 1638T/1638T follicular epithelial cells, thyroglobulin was mostly colocalized with calreticulin whereas in the Apc +/+ follicular epithelial cells, a significant amount of the cytoplasmic thyroglobulin did not colocalize with calreticulin. In addition, in thyroid-stimulating hormone (TSH)-treated Apc 1638T/1638T mice, electron microscopic analysis indicated less frequent pseudopod formation at the apical surface of the thyroid follicular cells than in Apc +/+ 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 of Apc 1638T/1638T mice and suggest suppressed secretory activities of these cells.
Key wordsAdenomatous polyposis coli (Apc) Apc1638T/1638T mice Thyroid gland Thyroid follicle Follicular epithelial cells Thyroglobulin Calreticulin
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