Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Mol Reprod Dev. 2012 Jul;79(7):488-98. doi: 10.1002/mrd.22057.
The mammalian cellular prion protein (PrP(C) ) is a highly conserved glycoprotein that may undergo conversion into a conformationally altered isoform (scrapie prion protein or PrP(Sc) ), widely believed to be the pathogenic agent of transmissible spongiform encephalopathies (TSEs). Although much is known about PrP(Sc) conversion and its role in TSEs, the normal function of PrP(C) has not been elucidated. In adult mammals, PrP(C) is most abundant in the central nervous tissue, with intermediate levels in the intestine and heart, and lower levels in the pancreas and liver. PrP(C) is expressed during neurogenesis throughout development, and it has recently been proposed that PrP(C) participates in neural cell differentiation during embryogenesis. In order to establish the developmental timing and to address the cell-specific expression of PrP(C) during mammalian development, we examined PrP(C) expression in bovine gametes and embryos through gestation Day 39. Our data revealed differential levels of Prnp mRNA at Days 4 and 18 in pre-attachment embryos. PrP(C) was detected in the developing central and peripheral nervous systems in Day-27, 32-, and -39 embryos. PrP(C) was particularly expressed in differentiated neural cells located in the marginal regions of the central nervous system, but was absent from mitotically active, periventricular areas. Moreover, a PrP(C) cell-specific pattern of expression was detected in non-nervous tissues, including liver and mesonephros, during these stages. The potential participation of PrP(C) in neural cell differentiation is supported by its specific expression in differentiated states of neurogenesis.
哺乳动物细胞朊病毒蛋白(PrP(C))是一种高度保守的糖蛋白,它可能会转化为构象改变的异构体(瘙痒朊病毒蛋白或 PrP(Sc)),广泛认为 PrP(Sc)是传染性海绵状脑病(TSEs)的致病因子。尽管人们对 PrP(Sc)转化及其在 TSEs 中的作用有了很多了解,但 PrP(C)的正常功能仍未阐明。在成年哺乳动物中,PrP(C)在中枢神经系统中含量最丰富,在肠道和心脏中含量中等,在胰腺和肝脏中含量较低。PrP(C)在整个发育过程中的神经发生过程中表达,最近有人提出 PrP(C)在胚胎发生期间参与神经细胞分化。为了确定发育时间,并解决哺乳动物发育过程中 PrP(C)的细胞特异性表达问题,我们通过妊娠第 39 天检查了牛配子和胚胎中的 PrP(C)表达。我们的数据显示,在着床前胚胎的第 4 天和第 18 天,Prnp mRNA 的水平存在差异。在第 27 天、32 天和 39 天的胚胎中,发育中的中枢和周围神经系统中检测到 PrP(C)。PrP(C)在中枢神经系统的边缘区域的分化神经细胞中表达特别明显,但在有丝分裂活跃的脑室周围区域不存在。此外,在这些阶段,在非神经组织中,包括肝脏和中肾,也检测到 PrP(C)细胞特异性表达模式。PrP(C)在神经发生的分化状态中的特异性表达支持了其在神经细胞分化中的潜在参与。