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We have analyzed the changes in isoform-specific mRNAs in the
transition from the fetal to the neonatal state. Of special
interest was the finding that although the TRa1 mRNA could be
identified by us as early as fetal day 17 we were unable to
identify the TRb1 mRNA until after birth. After birth the level
of TRb1 rose in an exponential fashion. In comparison the
postnatal rise in TRa1 was modest and only transient, showing an
increase of less than two-fold. These findings raised the
possibility that TRb1 isoform was specifically involved in
regulating the expression of the brain genes. We therefore set
about to determine whether or not we could detect a corresponding
rise in an isoform receptor protein.
In collaboration with Dr. Nicholas Ling we developed antisera specific for each of the receptor isoforms. This allowed us both to define by immunohistochemical technique the cells containing a specific receptor protein and to determine the relative content of individual tissue by determining the T3 nuclear binding capacity of individual tissue extracts both before and after immunoprecipitating the extract. The contribution of an individual receptor isoform could be calculated from the difference in the total binding capacity of a given tissue and the binding capacity after immunoprecipitation of the specific receptor isoform. The results of these studies showed a clear correlation between mRNA and isoform-specific binding capacity in the various tissues analyzed. Again, we could demonstrate TRa1 but not TRb1 receptor in rat fetus. These considerations led us to propose that TRb1 isoform is specifically involved in the brain gene differentiation. |
