An orphan nuclear receptor, mROR alpha, and its spatial expression in adult mouse brain

We have cloned cDNA encoding a mouse nuclear receptor mROR alpha which is a homolog of human retinoic acid receptor-related orphan receptor (hROR alpha). Cotransfection experiments revealed that mROR alpha activates transcription through a retinoic acid responsive element of the laminin B1 gene (lamRARE), but not through a RARE of RAR beta gene (beta RARE) or a synthetic palindromic thyroid hormone responsive element (TREpal). The most distal AGGTCA half-site among the three half-sites of lamRARE was sufficient for binding of mROR alpha and consequently for activation of transcription. Transactivation by mROR alpha was dependent on serum in culture medium after transfection, suggesting the presence of a possible ligand. Northern hybridization and in situ hybridization analyses revealed that mROR alpha is expressed in specific areas of the brain including thalamus and olfactory bulb as well as cerebellum where it is present at highest levels in Purkinje cells. In addition to regionally heterogeneous expression in brain, its expression was temporally regulated during differentiation of P19 cells into neural cells, but not into muscle cells. These observations suggest that mROR alpha plays important roles as a transcription factor not only in differentiation of neural cell lineages but also in the mature brain.