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 Apc1638T/1638T mice that express a truncated Apc lacking the C-terminal domain. The Apc1638T/1638T mice were tumor free and exhibited growth retardation. We recently reported abnormalities in thyroid morphology and functions of Apc1638T/1638T mice, although the mechanisms underlying these abnormalities are not known. In the present study, we further compared thyroid gland morphology in Apc1638T/1638T and Apc+/+ mice. The diameters of thyroid follicles in the left and right lobes of the same thyroid gland of Apc1638T/1638T mice were signifi cantly different whereas the Apc+/+ mice showed no signifi cant 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 Apc1638T/1638T follicular epithelial cells, thyroglobulin was mostly colocalized with calreticulin whereas in the Apc+/+follicular epithelial cells, a signifi cant amount of the cytoplasmic thyroglobulin did not colocalize with calreticulin. In addition, in thyroid-stimulating hormone (TSH)-treated Apc1638T/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 Apc1638T/1638T mice and suggest suppressed secretory activities of these cells.
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
- Molecular Biology