mortality/aging
• time of death ranges from as early as 9 days of age to over 22 weeks
• mice treated with T4 show a regression of symptoms after a 4-5 day delay, with disappearance of stridor and the return of normal weight, however, after an asymptomatic period of 33 days on average, dyspnea reappears progressively and mice die rapidly
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endocrine/exocrine glands
• thymus is frequently hypoplastic
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• enlargement of the thyroid which compresses both the trachea and the esophagus
• thyroid is already enlarged at 1 day after birth and mice develop a goiter
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• despite continuous T4 treatment, mice develop moderately to poorly differentiated thyroid adenocarcinomas, with persistence of cell polarity and the presence of microfollicles between the densely packed cells resembling anaplastic thyroid tumors
• thyroids exhibit dedifferentiation and disorganization, rapidly followed by the development of numerous tumor nodules
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• thyroid surface of older mice frequently shows large nodules and hemorrhagic cysts
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• mice are hypothyroid
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• organification of iodide is reduced
• however, iodine uptake is maintained in proportion to the gland weight
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growth/size/body
• short bulging forehead
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• short bulging forehead
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• thyroid surface of older mice frequently shows large nodules and hemorrhagic cysts
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• mice develop progressive cachexia due to reduced food intake because of compression of the trachea and esophagus by enlarged thyroid
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• growth delay
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hematopoietic system
• thymus is frequently hypoplastic
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• spleen is frequently hypoplastic
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homeostasis/metabolism
immune system
• thymus is frequently hypoplastic
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• spleen is frequently hypoplastic
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craniofacial
• short bulging forehead
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• short bulging forehead
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neoplasm
• despite continuous T4 treatment, mice develop moderately to poorly differentiated thyroid adenocarcinomas, with persistence of cell polarity and the presence of microfollicles between the densely packed cells resembling anaplastic thyroid tumors
• thyroids exhibit dedifferentiation and disorganization, rapidly followed by the development of numerous tumor nodules
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• thyroid tumors metastasize into the trachea, skeletal muscle, and lung
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respiratory system
• the epithelium of the trachea appears pluristratified, indicating chronic irritation
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• mice develop dyspnea and inspiratory stridor
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• compression of the trachea and esophagus due to enlarged thyroid gland, accompanied by dyspnea, inspiratory stridor and dysphagia, lead to progressive cachexia and premature death
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