Kim Y W, Sharma R P
Center for Environmental Toxicology, Utah State University, Logan, USA.
Reprod Toxicol. 1995 Sep-Oct;9(5):435-47. doi: 10.1016/0890-6238(95)00036-a.
Retinoids have pleiotropic effects on animal development. The eventual targets of retinoids are retinoic acid receptors (RARs). Therefore, developmental expression patterns of RARs are important in elucidating the mechanisms of normal functions of retinoids and retinoid-induced teratogenesis. We developed monospecific polyclonal antibodies against hRAR alpha, hRAR beta, and mRAR gamma, to study the developmental expression of RARs in hamster fetus. There was high sequence homology across the species for each subtype of RARs and antibodies raised against human or mouse RARs reacted with hamster RARs. In addition, hamster cDNA of RARs, which can generate the whole length antisense RNA probe using a suitable vector, were also isolated from a 12-day-old hamster fetal library. Monospecific antibodies and antisense RNA probes were used to localize proteins and transcripts of RARs in the developing hamster fetus from day 8 to day 14. There was a widespread distribution of RAR proteins and transcripts in the developing fetus. Expression was abundant in neuroepithelium, branchial arch, cardiac linings, and primordial bone and cartilage tissues. Overlapping expression and redundancy of various RARs may be one of the safeguard mechanisms in retinoid homeostasis.
维甲酸对动物发育具有多效性作用。维甲酸的最终作用靶点是维甲酸受体（RARs）。因此，RARs的发育表达模式对于阐明维甲酸正常功能机制以及维甲酸诱导的致畸作用机制至关重要。我们制备了针对人RARα、人RARβ和小鼠RARγ的单特异性多克隆抗体，以研究仓鼠胎儿中RARs的发育表达情况。RARs的每个亚型在不同物种间具有高度的序列同源性，针对人或小鼠RARs制备的抗体可与仓鼠RARs发生反应。此外，还从12日龄的仓鼠胎儿文库中分离出了RARs的仓鼠cDNA，该cDNA可利用合适的载体产生全长反义RNA探针。利用单特异性抗体和反义RNA探针，对发育中第8天至第14天的仓鼠胎儿的RARs蛋白和转录本进行定位。在发育中的胎儿中，RAR蛋白和转录本分布广泛。在神经上皮、鳃弓、心脏内膜以及原始骨和软骨组织中表达丰富。各种RARs的重叠表达和冗余可能是维甲酸稳态中的一种保护机制。
