| We next considered the possibility the surge in TRb1 initiated neonatal brain development. As we have emphasized above, the fetal brain contains substantial levels of TRa1 but virtually no TRb1. Thus, it appeared reasonable to consider the possibility that the thyroid hormone-dependent developmental process is initiated by TRb1. A definitive test of this concept became possible with the development of a TRb1 knock-out mouse by Forrest and colleagues (7), a preparation in which the TRb1 receptor has been functionally inactivated. Immunoprecipitation studies in our laboratory confirmed the absence of TRb1 protein. However, we were frankly disappointed to note that there was no detectable difference in the Pcp2 and MBP developmental profiles when knock-out and appropriately paired animals were compared. We concluded that TRb1 is not essential in mediating the effect of thyroid hormone in accelerating the expression of the Pcp-2 and myelin basic protein genes. |
