Payer Bernhard, Saitou Mitinori, Barton Sheila C, Thresher Rosemary, Dixon John P C, Zahn Dirk, Colledge William H, Carlton Mark B L, Nakano Toru, Surani M Azim
Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
Curr Biol. 2003 Dec 2;13(23):2110-7. doi: 10.1016/j.cub.2003.11.026.
stella is a novel gene specifically expressed in primordial germ cells, oocytes, preimplantation embryos, and pluripotent cells. It encodes a protein with a SAP-like domain and a splicing factor motif-like structure, suggesting possible roles in chromosomal organization or RNA processing. Here, we have investigated the effects of a targeted mutation of stella in mice. We show that while matings between heterozygous animals resulted in the birth of apparently normal stella null offspring, stella-deficient females displayed severely reduced fertility due to a lack of maternally inherited Stella-protein in their oocytes. Indeed, we demonstrate that embryos without Stella are compromised in preimplantation development and rarely reach the blastocyst stage. stella is thus one of few known mammalian maternal effect genes, as the phenotypic effect on embryonic development is mainly a consequence of the maternal stella mutant genotype. Furthermore, we show that STELLA that is expressed in human oocytes is also expressed in human pluripotent cells and in germ cell tumors. Interestingly, human chromosome 12p, which harbours STELLA, is consistently overrepresented in these tumors. These findings suggest a similar role for STELLA during early human development as in mice and a potential involvement in germ cell tumors.
斯黛拉（Stella）是一种在原始生殖细胞、卵母细胞、植入前胚胎和多能细胞中特异性表达的新基因。它编码一种具有类SAP结构域和类剪接因子基序结构的蛋白质，提示其在染色体组织或RNA加工中可能发挥作用。在此，我们研究了小鼠中斯黛拉基因靶向突变的影响。我们发现，杂合动物之间的交配产生了看似正常的斯黛拉基因敲除后代，但斯黛拉基因缺陷的雌性由于其卵母细胞中缺乏母源遗传的斯黛拉蛋白，生育力严重降低。事实上，我们证明没有斯黛拉的胚胎在植入前发育中受到损害，很少能发育到囊胚阶段。因此，斯黛拉是少数已知的哺乳动物母体效应基因之一，因为对胚胎发育的表型影响主要是母体斯黛拉突变基因型的结果。此外，我们表明在人类卵母细胞中表达的斯黛拉在人类多能细胞和生殖细胞肿瘤中也有表达。有趣的是，携带斯黛拉基因的人类12号染色体p臂在这些肿瘤中一直过度表达。这些发现表明斯黛拉在人类早期发育中与在小鼠中具有相似的作用，并可能参与生殖细胞肿瘤的发生。
