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

在这项研究中，我们试图直接调查的重要性，主要组织相容性复合体（MHC）抗原表达的调控作为成功妊娠所需的机制。为了研究转基因小鼠是否会被母体排斥，将人胎盘上表达的c-fos或b-actin基因的调控区和H-2K_b基因的编码区分别构建成嵌合基因，并在小鼠胎盘滋养层细胞上表达MHC抗原。显微注射这些基因。制作了30只创始人小鼠。在9只建立者小鼠的外周血有核细胞上检测到H-2K_b抗原表达。然而，它们的雄性和H-2K^b阴性雌性之间的交配导致了相似数量的转基因阳性和阴性F1小鼠没有表明胎儿排斥的症状，这可能是由于滋养层上缺乏转基因表达导致了它们的母亲没有排斥转基因胎儿。因此，切除胎盘和胎仔并用抗H-2K_b抗体进行组织学染色。在转基因阳性胎儿的胎盘滋养层细胞上未检测到H-2K^b抗原。人绒毛膜促性腺激素（human chorionic gonadotropin，hCG）是妊娠早期由滋养层细胞合成和分泌的妊娠特异性激素。将hCG-β基因5'端调控区与H-2K_b基因编码区连接，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.