抄録
Abnormal cerebellar development of staggerer (sg) mouse has been reported due to the mutation of retinoic acid receptor-related orphan nuclear receptor (ROR)α, a member of the steroid, thyroid, and retinoid receptor superfamily. However, the role of RORα on cerebellar development has not yet been clarified. The appropriate mRNA levels of neurotrophins and their receptors are necessary for development of cerebellum. However, the changes in expressions of these genes in sg mouse cerebellum have not yet been studied. To understand whether neurotrophins and their receptors are involved in cerebellar impairments of sg mouse, we investigated these gene expression profiles during postnatal development by RT-PCR and in situ hybridization. The decreased mRNA levels of BDNF, NT-3 and NT-4 at P15 or P21 and increased mRNA levels of NGF, TrkA and TrkB were shown in homozygous sg mouse compared with those in wild type. Interestingly, the expression patterns of these mRNA in sg mouse are similar to those in hypothyroid animals, suggesting a possible cross-talk between RORα and thyroid hormone receptors. The hybridization signals for BDNF, NT-3 and TrkB mRNAs were mostly located in the granule cells, suggesting the important roles of neurotrophins in granule cells during sg postnatal development. These results indicate that the mutation of RORα alters the expression of neurotrophins and their receptors, which may be partly responsible for abnormal cerebellar development of sg mouse. [J Physiol Sci. 2006;56 Suppl:S215]