Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors.

Background: Thyroid hormone (TH) plays a key role in the developing brain, including the cerebellum. TH deficiency induces organizational changes of the cerebellum, causing cerebellar ataxia. However, the mechanisms causing these abnormalities are poorly understood. Various animal models have been used to study the mechanism. Lacking dual oxidase (DUOX) and its maturation factor (DUOXA) are major inducers of congenital hypothyroidism. Thus, this study examined the organizational changes of the cerebellum using knockout mice of the Duoxa gene (Duoxa–/–). Methods: The morphological, behavioral, and electrophysiological changes were analyzed in wild type (Wt) and Duoxa-deficient (Duoxa–/–) mice from postnatal day (P) 10 to P30. To detect the changes in the expression levels of presynaptic proteins, Western blot analysis was performed. Results: The proliferation and migration of granule cells was delayed after P15 in Duoxa–/– mice. However, these changes disappeared by P25. Although the cerebellar structure o...