Transgenic indicator mice for studying activated retinoic acid receptors during development

Ayne Balkan, Melissa Colbert, Cheryl Bock, Elwood Linney

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Retinoic acid (RA) receptors (RARs) are li-gand-inducible transcription factors that bind to specific DNA sequences associated with the regulatory regions of RAregulatable genes. Since RA has been implicated as an important factor both in normal development and in teratological studies, one would like to have a model system that detects the presence of activated receptors during development. We have constructed a recombinant reporter gene that has three copies of the RA response element (RARE) from the RARβ-2 proer 5′ to the herpes simplex virus thymidine kinase pro; this regulatory region is coupled to the bacterial β-gatosidase reporter gene. This construct was RA inducible in transient transfection assays in F9 embryonal carcinoma cells. Transgenic embryos with this reporter gene construct exhibited tricted and reproducible patterns of β-galactosidase activity during embryogenesis, beginning between gestational ages day 7.5 and 8.5. At day 8.5, β-galactosidase activity was detected in the closed neurotube and somites. Day 8.5 embryos, from pegnant females fed RA 14 hr earlier, exhibited a greater intensity and distribution of β-galactosidase activity. Similarly, at later stages of gestation, maternal RA exposure resulted in enhanced embryonic β-galactosidase expression. This type of transgenic indicator mouse should be useful in detailing the role of activated RARs during embryonic development.

Original languageEnglish (US)
Pages (from-to)3347-3351
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number8
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

Keywords

  • Differentiation
  • Mouse embryos
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • General

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