IN addition to having profound effects on embryonic pattern formation1-5, retinoic acid (RA) has striking effects on differentiation and maintenance of epithelial cells in vivo and in vivo (reviewed in refs 6 and 7). Skin is a major target organ for retinoids both in its normal6-9 and pathological states10. The discovery of two human nuclear receptors for RA (hRARα and hRARβ) acting as transcriptional RA-inducible enhancer factors11-14 has provided a basis for understanding how RA controls gene expression15,16. To investigate the specific role that RARs might play during development and in adult tissues, we have cloned the mouse RARα and RARβ (mRARα and mRARβ). Their amino-acid sequences are much more homologous to those of hRARα and hRARβ, respectively, than to each other, which suggests strongly that RARα- and β-subtypes have different functions. Most interestingly we have discovered a novel RAR subtype (mRAR-γ) whose expression in adult mouse seems to be highly restricted to skin, whereas RARα and RARβ are expressed in a variety of adult tissues. Furthermore, both mRARα and mRARγRNAs are readily detected in undifferentiated F9 embryocarcinoma (EC) cells, whereas mRARβ messenger RNA is induced at least 30-fold in RA-differentiated F9 cells.
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