Solomin L, Johansson C B, Zetterström R H, Bissonnette R P, Heyman R A, Olson L, Lendahl U, Frisén J, Perlmann T
The Ludwig Institute for Cancer Research, Stockholm Branch, Sweden.
Nature. 1998 Sep 24;395(6700):398-402. doi: 10.1038/26515.
Retinoids regulate gene expression through the action of retinoic acid receptors (RARs) and retinoid-X receptors (RXRs), which both belong to the family of nuclear hormone receptors. Retinoids are of fundamental importance during development, but it has been difficult to assess the distribution of ligand-activated receptors in vivo. This is particularly the case for RXR, which is a critical unliganded auxiliary protein for several nuclear receptors, including RAR, but its ligand-activated role in vivo remains uncertain. Here we describe an assay in transgenic mice, based on the expression of an effector fusion protein linking the ligand-binding domain of either RXR or RAR to the yeast Gal4 DNA-binding domain, and the in situ detection of ligand-activated effector proteins by using an inducible transgenic lacZ reporter gene. We detect receptor activation in the spinal cord in a pattern that indicates that the receptor functions in the maturation of limb-innervating motor neurons. Our results reveal a specific activation pattern of Gal4-RXR which indicates that RXR is a critical bona fide receptor in the developing spinal cord.
维甲酸通过维甲酸受体（RARs）和维甲酸X受体（RXRs）的作用来调节基因表达，这两种受体都属于核激素受体家族。维甲酸在发育过程中至关重要，但一直难以评估配体激活受体在体内的分布情况。对于RXR来说尤其如此，它是包括RAR在内的几种核受体的关键非配体辅助蛋白，但其在体内配体激活的作用仍不确定。在这里，我们描述了一种在转基因小鼠中的检测方法，该方法基于将RXR或RAR的配体结合域与酵母Gal4 DNA结合域连接的效应融合蛋白的表达，以及通过使用可诱导的转基因lacZ报告基因对配体激活的效应蛋白进行原位检测。我们在脊髓中检测到受体激活，其模式表明该受体在支配肢体的运动神经元成熟过程中发挥作用。我们的结果揭示了Gal4-RXR的特定激活模式，表明RXR是发育中的脊髓中的关键真正受体。
