Fawcett D, Pasceri P, Fraser R, Colbert M, Rossant J, Giguère V
Division of Endocrinology, Hospital for Sick Children, Toronto, Canada.
Development. 1995 Mar;121(3):671-9. doi: 10.1242/dev.121.3.671.
The cytoplasmic retinoic acid (RA)-binding protein CRABP-II is expressed widely throughout early morphogenesis in mouse embryo, but its expression becomes more restricted as organogenesis progresses. CRABP-II expression remains strong in the developing limb bud suggesting a role for this protein in limb patterning. Here, we show that the CRABP-II promoter can direct expression of a lacZ transgene in a specific posterior domain during limb bud development. In order to investigate in more detail the role played by CRABP-II in RA signal transduction, we have also generated mice homozygous for a null mutation of this gene. CRABPII-/- mice are viable and fertile but show a developmental defect of the forelimb, specifically an additional, postaxial digit. This digit is generally, but not exclusively, limited to a single forepaw of an individual animal. The penetrance of the phenotype varies according to the genetic background, occurring most frequently on the inbred 129Sv background (50%), less frequently on the C57Bl/6 background (30%) and rarely on the outbred CD1 background (10%). This developmental abnormality implies a role for CRABP-II in normal patterning of the limb.
细胞质视黄酸（RA）结合蛋白CRABP-II在小鼠胚胎的早期形态发生过程中广泛表达，但随着器官发生的进展，其表达变得更加局限。CRABP-II在发育中的肢芽中表达仍然很强，表明该蛋白在肢体模式形成中发挥作用。在这里，我们表明CRABP-II启动子可以在肢芽发育过程中指导lacZ转基因在特定的后部区域表达。为了更详细地研究CRABP-II在RA信号转导中所起的作用，我们还培育了该基因纯合缺失突变的小鼠。CRABPII-/-小鼠存活且可育，但表现出前肢的发育缺陷，特别是额外的轴后指。这个指通常但不限于单个动物的单个前爪。表型的外显率根据遗传背景而变化，在近交129Sv背景上最常见（50%），在C57Bl/6背景上较不常见（30%），在远交CD1背景上很少见（10%）。这种发育异常意味着CRABP-II在肢体的正常模式形成中发挥作用。
