AN ORPHAN NUCLEAR RECEPTOR, MROR-ALPHA, AND ITS SPATIAL EXPRESSION INADULT-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 acti vates transcription through a retinoic acid responsive element of the laminin B1 gene (lamRARE), but not through a RARE of RAR beta gene (be ta 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 dep endent on serum in culture medium after transfection, suggesting the p resence of a possible ligand. Northern hybridization and in situ hybri dization analyses revealed that mROR alpha is expressed in specific ar eas of the brain including thalamus and olfactory bulb as well as cere bellum where it is present at highest levels in Purkinje cells. In add ition to regionally heterogeneous expression in brain, its expression was temporally regulated during differentiation of P19 cells into neur al cells, but not into muscle cells. These observations suggest that m ROR alpha plays important roles as a transcription factor not only in differentiation of neural cell lineages but also in the mature brain.