Balkan W, Klintworth G K, Bock C B, Linney E
Department of Microbiology and Immunology, Duke University, Durham, North Carolina 27710.
Dev Biol. 1992 Jun;151(2):622-5. doi: 10.1016/0012-1606(92)90200-z.
Retinoic acid receptors (RARs) modulate gene expression following association with retinoic acid (RA). In transient transfection, an RAR alpha-beta-galactosidase fusion protein (RAR-LacZ) was able to transactivate expression in the absence of RA. When expressed in the ocular lens of transgenic mice, this constitutively active RAR-LacZ fusion gene resulted in founder and progeny animals that exhibited cataracts and microphthalmia, both being characteristics of retinoid-induced teratogenesis. The transgenic phenotypes indicate that retinoid teratogenesis can be mimicked by expression of a constitutively active RAR-LacZ fusion protein in retinoid-sensitive tissues.
维甲酸受体(RARs)与维甲酸(RA)结合后可调节基因表达。在瞬时转染中,RARα-β-半乳糖苷酶融合蛋白(RAR-LacZ)在无RA的情况下能够反式激活表达。当在转基因小鼠的晶状体中表达时,这种组成型活性RAR-LacZ融合基因导致了出现白内障和小眼症的奠基者动物和后代动物,这两者都是类视黄醇诱导的致畸作用的特征。转基因表型表明,在类视黄醇敏感组织中表达组成型活性RAR-LacZ融合蛋白可模拟类视黄醇致畸作用。