Retinoic acid receptor beta 2 mRNA is elevated by retinoic acid in vivo in susceptible regions of mid-gestation mouse embryos.
Many of the biological effects of retinoic acid are mediated by its nuclear receptors (RAR-alpha, RAR-beta, and RAR-gamma), and each of these three receptors exist in multiple isoforms. As a first step to identify if any of the receptor isoforms are involved in dysmorphogenesis which is induced in mouse embryos after treatment with retinoic acid (RA), we examined the levels of mRNA of several isoforms of each RAR in the limb buds and other embryonic regions of normal and RA-treated embryos. Within 3 to 6 hr after treatment of mice on day 11 of gestation with RA, RAR-beta 2 mRNA levels in the whole embryo increased 7-fold while both RAR-alpha 2 and RAR-gamma 1 mRNA levels were elevated only 2-fold. Since RA treatment of day 11 embryos especially produces limb defects in virtually every embryo, we next examined individual embryonic regions separately. Limb buds showed the highest elevations in RAR-beta 2 mRNA levels (12-fold) compared to a moderate elevation in the head/craniofacial region (8-fold) and a small elevation in the remainder of the body (4-fold). In contrast, RAR-alpha 2 and RAR-gamma 1 mRNA levels were elevated in all these tissues to a similar extent, which amounted to only about a 2-fold increase. Retinol, the precursor of RA in the embryo, was also capable of elevating RAR-beta 2 mRNA levels in the limb bud, but the increase was delayed, apparently indicating that metabolic conversion of retinol to RA preceded the effect on mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Harnish
D C
DC
Department of Biochemistry, Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Jiang
H
H
Soprano
K J
KJ
Kochhar
D M
DM
Soprano
D R
DR
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005314:Embryonic and Fetal Development; D005865:Gestational Age; D007536:Isomerism; D051379:Mice / Q000196:embryology; D012333:RNA, Messenger / Q000378:metabolism*; D018168:Receptors, Retinoic Acid; D013723:Teratogens / Q000494:pharmacology; D014018:Tissue Distribution; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology
D002352:Carrier Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D013723:Teratogens; D014801:Vitamin A; D014212:Tretinoin