Abstract
The deletion of RORα, a retinoic acid receptor-related orphan nuclear receptor induces a characteristic severe cerebellar ataxia and early death around postnatal 3 weeks in Staggerer(sg) mouse. The vital function of RORα during biological processes is questioned. RORα action is mediated by binding to DNA sequence called ROR response element (RORE) to regulate expression of the target gene. Interestingly, the morphology of Purkinje cell in sg appears almost similar to that of hypothyroid mouse. Thus, we hypothesized that there may be an interaction between RORα and thyroid hormone receptors (TRs). To understand whether mRNA levels of neurotrophins and their receptors in sg mouse are similar to those in hypothyroid mouse or not, we investigated the gene expression patterns in the developing cerebellum of sg mouse by RT-PCR. An evident alteration in expression levels of NGF, BDNF, NT-3 and their receptors TrkA, B, C in cerebellum due to RORα mutation was observed. NGF, TrkA and TrkB showed significantly higher levels in homozygous sg mouse than those in both heterozygote and wild at postnatal 15 days. The expression levels of BDNF and NT-3 were lower at postnatal 15 or 21 days compared to those of wild type animal. Our results indicate that the expression patterns of neurotrophins and their receptors during cerebellar development of both sg mouse and hypothyroid mouse are very much alike. The cross talk between ROR and TR could exist in vivo. [Jpn J Physiol 55 Suppl:S210 (2005)]
