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 3.0kb transcript was observed in testis and brain, but not liver or lung RNA. In the brain the 3.0kb 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 7.2kb 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 7.2kb 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.
|Original language||English (US)|
|Number of pages||9|
|Journal||International Journal of Developmental Neuroscience|
|State||Published - Aug 2003|
Bibliographical noteFunding Information:
The authors express their appreciation to Drs. Raul Urrutia, Tiffany Cook, Mark McNiven, and Hong Cao for helpful suggestions and criticisms and to Cheri Mueske and Daniel Oas for technical assistance. This work was supported by a Thyroid Research Advisory Council grant from Knoll Pharmaceuticals (NLE). Andrew M. Arnold was supported by a Postdoctoral Training Grant in Endocrinology and Metabolism from the National Institutes of Health (T32 DK07352).
- Brain development
- Gene regulation
- Thyroid hormone