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The mutant <jats:italic>hyt\/hyt<\/jats:italic> mouse, characterized by fetal\u2010onset, life\u2010long hypothyroidism resulting from a point mutation of the thyroid\u2010stimulating hormone receptor of the thyroid gland, displays a variety of abnormalities in motor behavior that are likely associated with dysfunctions of specific brain regions and a defective corticospinal tract (CST). To test the hypothesis that fetal and neonatal hypothyroidism cause abnormal CST development, the growth of the CST was investigated in hypothyroid <jats:italic>hyt\/hyt<\/jats:italic> mice and their euthyroid progenitors, the BALB\/cByJ mice. Anterograde labeling with biotinylated dextran amine demonstrated a decrease in the number of CST axons in the <jats:italic>hyt\/hyt<\/jats:italic> mouse at the first lumbar level at postnatal day (P) 10. After retrograde tracing with fast blue (FB), fewer FB\u2010labeled neurons were found in the motor cortex, the red nucleus, and the lateral vestibular nucleus of the <jats:italic>hyt\/hyt<\/jats:italic> mouse. At the fourth lumbar level, the <jats:italic>hyt\/hyt<\/jats:italic> mouse also showed smaller CST cross\u2010sectional areas and significantly lower numbers of unmyelinated axons, myelinated axons, and growth cones within the CST during postnatal development. At P10, the <jats:italic>hyt\/hyt<\/jats:italic> mouse demonstrated significantly lower immunoreactivity of embryonic neural cell adhesion molecule in the CST at the seventh cervical level, whereas the expression of growth\u2010associated protein 43 remained unchanged. Our study demonstrated an abnormal development of the CST in the <jats:italic>hyt\/hyt<\/jats:italic> mouse, manifested by reduced axon quantity and retarded growth pattern at the lumbar spinal cord. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21750","type":"journal-article","created":{"date-parts":[[2008,6,9]],"date-time":"2008-06-09T23:47:47Z","timestamp":1213055267000},"page":"3126-3139","source":"Crossref","is-referenced-by-count":6,"title":["Abnormal growth of the corticospinal axons into the lumbar spinal cord of the <i>hyt\/hyt<\/i> mouse with congenital hypothyroidism"],"prefix":"10.1002","volume":"86","author":[{"given":"Jung\u2010Yu C.","family":"Hsu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart 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