Thyroid-specific enhancer-binding protein (T/EBP), also called thyroid transcription factor 1 (TTF1) or NKX2.1, is a homeodomain transcription factor that plays a role in regulating expression of thyroid and lung-specific genes as well as genesis of the thyroid, lung, and ventral forebrain. The thyroid and lung-specific genes that are regulated by T/EBP are those encoding thyroid peroxidase, thyroglobulin, and TSH receptor, and those encoding surfactant proteins A, B, and C, and Clara cell secretory protein, respectively. The essential role of T/EBP for organogenesis was unequivocally demonstrated by the T/ebp-null mouse that is missing the thyroid and pituitary, and has severe defects in the lung and hypothalamus. Thus, it appears that T/EBP is a master regulatory gene involved in the genesis of these organs by either directly or indirectly activating or suppressing downstream target genes. Current efforts focused on identifying genes that are regulated by T/EBP and that are involved in thyroid and lung organogenesis. To this end, thyroids or lungs were collected from T/ebp-null mouse and wild-type littermate embryos. Laser capture microdissection (LCM) was employed to isolate as tiny tissue as the thyroid primordium. Total RNAs prepared from LCM microdissected thyroid primordia or embryo lungs were subjected to DNA microarrays. Several candidate genes were obtained that appear to be differentially expressed in the thyroid primodium or the lung between T/ebp-null and wild-type mouse embryos. RT-PCR and in situ hybridization have been used to confirm their differential expressions in embryonic thyroid primordium or lung. In order to understand the role of T/EBP during development and in homeostasis of the thyroid, a conditional knockout mouse line that deletes T/EBP expression only in the thyroid has been developed. Various aged mouse thyroids with and without T/EBP deletion are examined by histopathological analysis and immunohistochemistry using antibodies against T/EBP and thyroglobulin. Detailed analyses are currently in progress.
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