Aberrant Cerebellar Development of Transgenic Mice Expressing Dominant-Negative Thyroid Hormone Receptor in Cerebellar Purkinje Cells

• DOI: 10.1210/en.2014-1079
• Publication Date: 2015-01-20T17:41:07Z
• Authors: Lu Yu; Toshiharu Iwasaki; Ming Xu; Ronny Lesmana; Yu Xiong; Noriaki Shimokawa; William W. Chin; Noriyuki Koibuchi
• Keywords: 0301 basic medicine; Receptors, Thyroid Hormone; Mice, Transgenic; Dendrites; 3. Good health; Mice; Purkinje Cells; 03 medical and health sciences; Cell Movement; Motor Skills; Cerebellum; Rotarod Performance Test; Animals

To study the role of thyroid hormone (TH) in cerebellar development, we generated transgenic mice expressing a dominant-negative TH receptor (TR) Purkinje cells. A mutant human TRβ1 (G345R), which binds to TH-response element but cannot bind T3, was subcloned into exon 4 full-length L7/Pcp-2 gene, is specifically expressed and retinal rod bipolar The transgene cells postnatal cerebellum. cell dendrite arborization significantly delayed mice. Surprisingly, granule migration also delayed. In primary culture, TH-induced suppressed. quantitative real-time RT-PCR analysis, expression levels several TH-responsive genes were altered. inositol trisphosphate type 1 retinoic acid receptor-related orphan receptorα mRNAs, are mainly cells, brain-derived neurotrophic factor mRNA, both decreased. neurotrophin-3 hairless myelin basic protein oligodendrocytes, motor coordination disrupted. These results indicate that action through its binding TR required for normal development. important development other subsets such as oligodendrocytes.