Date of Completion
Jessica Costa-Guda; Andrew Arnold
Biology | Cancer Biology | Cell and Developmental Biology | Cell Biology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Developmental Biology | Diseases | Endocrine System Diseases | Endocrinology | Life Sciences | Medicine and Health Sciences | Neoplasms | Other Cell and Developmental Biology
Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a disease characterized by parathyroid tumors, renal cysts or tumors, uterine tumors, and ossifying jaw fibromas. The cause of this syndrome is linked to a tumor suppressor gene called Cdc73, which encodes the protein product parafibromin. The loss of proper expression of Cdc73/parafibromin is implicated in the development of the tumors typical of HPT-JT, although the exact mechanisms of tumorigenesis are unclear. In particular, not much is understood about the development of ossifying fibromas (OF) of the jaw in this syndrome. OF is a benign bone neoplasm that can affect the mandible and maxilla, and consists of fibrous tissue in place of bone. The goal of this research was to deepen the understanding of the role Cdc73/parafibromin plays in the development of OF through creating a mouse model of OF. Cdc73 loss was targeted to the cranial neural crest of the mouse. However, homozygous cranial neural knockouts of Cdc73 proved to be embryonic lethal. Investigation of these embryos revealed the presence of apoptosis in the mandible and the midbrain, the latter of which is the likely cause of lethality. This finding provides further evidence that the normal expression of Cdc73/parafibromin is required in embryonic development. Heterozygous null mice were viable and healthy. Histological analysis of their jaws revealed no development of OF, indicating that the development of these tumors requires biallelic inactivation of Cdc73. Parafibromin was detected throughout the jaw tissue, the presence of which is also consistent with a tumor suppressor model.
Shen, Lilia, "Embryonic Lethality of Cranial Neural Crest Deletion of Cdc73" (2019). Honors Scholar Theses. 742.
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