The CORT-GR signal transduction pathway and CORT-induced cleft palate in H-2 congenic mice.
A significant association between genes at or near the H-2 complex and glucocorticoid (CORT)-induced cleft palate in mice has been conclusively demonstrated. In addition, the frequency of CORT-induced cleft palate in heterozygous offspring from reciprocal crosses has been shown to be dependent on maternal H-2 haplotype. Although CORT responses are known to be mediated through the glucocorticoid receptor (GR), the involvement of H-2 haplotype-specific variation in the embryonic CORT-GR signal transduction pathway in CORT responsiveness remains uncertain. In this study, we characterized the embryonic (E13 to E15) CORT-GR pathway in developing B10 (H-2b) and B10.A (H-2a) mouse palates. Northern analysis demonstrates similar GR transcripts and mRNA steady-state levels in embryonic B10 and B10.A mouse palates. Palatal GR M(r) and pI, as determined by Western analysis, are similar between strains and among gestational days. We also analyzed possible haplotype-specific qualitative or quantitative differences in the ability of the GR to bind a glucocorticoid response element (GRE); no significant differences in the GR-GRE complex or in the levels of activated GR are seen between strains or among gestational days. Based on these results, we conclude that H-2 associated differences in susceptibility to CORT-induced cleft palate are not associated with either variation in embryonic GR or increasing gestational age. To determine if endogenous differences in maternal circulating corticosterone levels are related to differential embryonic CORT responsiveness, the levels of serum corticosterone were determined by RIA in pregnant dams on day 13 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)
Jaskoll
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Laboratory for Developmental Genetics, University of Southern California, Los Angeles 90089-0641, USA.
Choy
H A
HA
Chen
H
H
Melnick
M
M
D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002972:Cleft Palate / Q000139:chemically induced* / Q000196:embryology / Q000235:genetics; D003345:Corticosterone / Q000097:blood / Q000633:toxicity*; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006183:H-2 Antigens / Q000235:genetics* / Q000502:physiology; D006239:Haplotypes; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010159:Palate / Q000196:embryology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism; D014222:Triamcinolone Acetonide / Q000031:analogs & derivatives / Q000633:toxicity
D000893:Anti-Inflammatory Agents; D015342:DNA Probes; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D013255:Steroid 21-Hydroxylase; D014222:Triamcinolone Acetonide; C005900:triamcinolone hexacetonide; D003345:Corticosterone