THE T EBP NULL MOUSE THYROID-SPECIFIC ENHANCER-BINDING PROTEIN IS ESSENTIAL FOR THE ORGANOGENESIS OF THE THYROID, LUNG, VENTRAL FOREBRAIN, AND PITUITARY/

The thyroid-specific enhancer-binding protein (T/ebp) gene was disrupt ed by homologous recombination in embryonic stem cells to generate mic e lacking T/EBP expression. Heterozygous animals developed normally, w hereas mice homozygous for the disrupted gene were born dead and lacke d the lung parenchyma. Instead, they had a rudimentary bronchial tree associated with an abnormal epithelium in their pleural cavities. Furt hermore, the homozygous mice had no thyroid gland but had a normal par athyroid. In addition, extensive defects were found in the brain of th e homozygous mice, especially in the ventral region of the forebrain. The entire pituitary, including the anterior, intermediate, and poster ior pituitary, was also missing. In situ hybridization showed that the T/ebp gene is expressed in the normal thyroid, lung bronchial epithel ium, and specific areas of the forebrain during early embryogenesis. T hese results establish that the expression of T/EBP, a transcription f actor known to control thyroid-specific gene transcription, is also es sential for organogenesis of the thyroid, lung, ventral forebrain, and pituitary.