Hypothyroidism in early postnatal development leads to abnormal CNS development that may be controlled in part at the level of gene transcription. Comparing the expression of euthyroid (EuT) and hypothyroid (HypoT) rat brain mRNAs by differential display PCR (ddPCR), we identified a novel
dynamin III mRNA that was up-regulated in the hypothyroid state. Northern analysis of brain
mRNA using a probe from the
dynamin III open reading frame (ORF) revealed two transcripts of 3.0 and 7.2kb size. The 3.0 kb transcript was observed in testis and brain, but not liver or lung
RNA. In the brain the 3.0 kb transcript increased from 25 to 57% of adult (Ad) levels from postnatal day (p) p2-p15, but was not significantly regulated by
thyroid hormone status. In contrast, the more abundant 7.2 kb transcript increased from 16.8 to 48.0% of adult levels from p2 to p15 in euthyroid rat pups but from 54.0% of adult levels at p2 to 97.9% of adult levels by p15 in hypothyroid pups. Overlapping
cDNA clones from a rat brain cDNA library defined the 7.2kb
mRNA, which consisted of the complete ORF, containing a four
amino acid insert at the end of the pleckstrin homology domain (PHD), and two unique 3'-flanking regions, that are likely derived from alternative processing. Thus, the 7.2 kb
dynamin III transcript is brain-specific and selectively regulated by
thyroid hormone status. The data suggest that the regulation of
dynamin III by altered
thyroid hormone status may affect synaptogenesis in the CNS through
dynamin's essential roles in synaptic vesicle and receptor recycling,
neurotransmitter reuptake, and
growth factor receptor signaling.