Biological Significance of Specific Regulation in Major Histocompatibility Complex (MHC) Antigen Expression on Placenta

在这项研究中，我们试图直接研究主要组织相容性复合体（MHC）抗原表达的调节作为成功妊娠所需的机制的意义。通过在胎盘滋养细胞上表达MHC抗原的转基因小鼠，观察转基因胎儿是否被母体排斥。从人c-fos或b-actin基因在胎盘上表达的调控区和H-2K^b基因的对应区构建嵌合基因。这些构建的基因的显微注射。培育了30只创始人老鼠。9只小鼠外周有核细胞检测H-2K^b抗原的表达。然而，它们的雄性与H-2K^b阴性的雌性交配，导致转基因阳性和阴性的F1小鼠数量相似，没有出现排斥胎儿的症状。有一种可能是滋养细胞上缺乏转基因表达导致转基因胎儿没有被母体排斥。因此，切除胎盘和胎儿，用抗h - 2k ^b抗体进行组织学染色。转基因阳性胎儿胎盘滋养细胞未检测到H-2K^b抗原。此外，使用H-2K^b特异性序列的原位引物延伸分析未能显示H-2K^b mRNA的存在。人绒毛膜促性腺激素（hCG）是妊娠早期由滋养细胞合成和分泌的妊娠特异性激素。利用hcg - β基因5′侧调控区和H-2K^b基因对应区构建了一个新的嵌合基因。使用这种嵌合基因的转基因小鼠的生产正在进行中。我们为这些小鼠安排了上述筛选分析。

In this study we attempted to investigate directly the significance of regulation in major histocompatibility complex (MHC) antigen expression as a mechanism required for successful pregnancy. Transgenic mice expressing MHC antigens on trophoblasts of the placenta were produced to inquire whether transgenic fetuses are rejected by their mother or not.The chimerical genes were constucted from both the regulatory region of human c-fos or b-actin gene, which can be expressed on the placenta, and the cording region of H-2K^b gene. A microinjection of these constructed genes. produced 30 founder mice. H-2K^b antigen expression was detected on peripheral nucleated cells of 9 founder mice. However, the mating between their males and H-2K^b negative females resulted in a similar number of the transgene-positive and-negative F1 mice without symptoms indicating the rejection of feuses.There is the possibility that a lack of transgene expression on trophoblasts led to no rejection of transgenic fetuses by their mothers. Therefore, placentas together with fetuses were resected and subjected to a histological staining with anti-H-2K^b antibody. No H-2K^b antigens were detected on the placental trophoblasts of transgene-positive fetuses. Additionally, in situ primer extension analysis using H-2K^b specific scquence failed to show a presence of H-2K^b mRNA.Human chorionic gonadotropin (hCG) is the pregnancy-specific hormone synthesized and secreted by trophoblast cells from early pregnancy period. A new chimerical genc was thus constructed from the regulatory region of 5' side of hCG-beta gene and the cording region of H-2K^b gene. The production of transgenic mice using this chimerical gene is in progress. We schedule the screening analyzes described above for these mice.