Loss of PGC-specific expression of the orphan nuclear receptor ERR-β results in reduction of germ cell number in mouse embryos
Loss of PGC-specific expression of the orphan nuclear receptor ERR-β results in reduction of germ cell number in mouse embryos
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DOI：
10.1016/j.mod.2004.01.006
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发表时间：
2004-03-01
影响因子：
2.6
通讯作者：
Abe, K
中科院分区：
文献类型：
--
作者：
Mitsunaga, K;Araki, K;Abe, K
雌激素相关受体β(ERR-P)是一种孤儿核受体，特异表达于着床后胚胎外胚外胚层的一部分。Err-P对胎盘发育是必不可少的，因为Err-P缺失突变体由于胎盘异常而在10.5dpc死亡。在这里，我们发现Err-P在原始生殖细胞(PGC)中特异表达，这显然是另一种重要的生殖细胞类型。胚胎生殖细胞中Err-P基因的表达从胚胎发育到生殖器脊后的E11.5开始，并持续到雌雄生殖细胞的E15-E16。抗Err-P抗体免疫染色显示，Err-P蛋白在E11.5~E16.5的雄性和雌性性腺的生殖细胞中均有特异表达。为了研究err-P在PGC中的作用，我们用野生型四倍体胚胎补充了err-P缺失突变体的胎盘缺陷，并分析了挽救的胚胎中生殖细胞的发育。结果表明，ERR-P对性腺和生殖细胞的发育无明显影响，但生殖细胞数量明显减少，提示ERR-P可能参与了性腺生殖细胞的增殖。被抢救出来的胚胎可以发育到足月，并成长到成年。被拯救的err-P缺失男性被发现是可生育的，但男性和女性缺失突变体都表现出行为异常，这意味着Err-β在更广泛的生物过程中发挥着比之前认为的更重要的作用。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
Estrogen related receptor beta (ERR-P) is an orphan nuclear receptor specifically expressed in a subset of extra-embryonic ectoderm of post-implantation embryos. ERR-P is essential for placental development since the ERR-P null mutants die at 10.5 dpc due to the placenta abnormality. Here, we show that the ERR-P is specifically expressed in primordial germ cells (PGC), obviously another important cell type for reproduction. Expression of the ERR-P mRNA in embryonic germ cells started at E11.5 as soon as PGC reached genital ridges, and persisted until E15-E16 in both sexes. Immunostaining with anti-ERR-P antibody revealed that the ERR-P protein is exclusively expressed in germ cells in both male and female gonads from E11.5 to E16.5. To study function of the ERR-P in PGC, we complemented placental defects of the ERR-P null mutants with wild-type tetraploid embryos, and analyzed germ cell development in the rescued embryos. It was found that development of gonad and PGC was not apparently affected, but number of germ cells was significantly reduced in male and female gonads, suggesting that the ERR-P appears to be involved in proliferation of gonadal germ cells. The rescued embryos could develop to term and grow up to adulthood. The rescued ERR-P null male were found to be fertile, but both male and female null mutants exhibited behavioural abnormalities, implying that the ERR-beta plays important roles in wider biological processes than previously thought. (C) 2004 Elsevier Ireland Ltd. All rights reserved.