Cloning of Several Genes Coding for Retinoic Acid Nuclear Receptors in the Mouse Embryonal Carcinoma Cell Line PCC7–MZ1

Abstract

Mouse embryonal carcinoma cell line PCC7–Mz1 can be induced by retinoic acid (RA) to differentiate into several well defined phenotypes of neuroectodermal origin (Lang, E. et al. (1989) J. Cell. Biol. 109, 2481–2493). Several subclones of the cell line (clonal variants) differ from each other in their developmental potential. To test whether these differences in cellular fate are due to somatic mutations in specific genes of these cells, we have cloned full length cDNAs coding for the α₁ and β₂ isoforms, and partial length cDNAs coding for the α₂ β₁ and β₃ isoforms of the retinoic acid nuclear receptór (RAR). The cloned cDNAs did not differ in sequence from those of normal mouse cells. Using as probe the β₂–RAR promotor region from mouse liver, we also checked for restriction fragment length polymorphism in the promotor regions of RA-inducible and RA-resistent cell variants. No alterations in this region of RAR genes was found in the clonal variants tested. The different patterns of derivatives produced by the variants upon exposure to RA therefore cannot be caused by somatic mutations in RAR genes of the tumor cell lines.