ACTIVIN/INHIBIN BETA-B SUBUNIT GENE DISRUPTION LEADS TO DEFECTS IN EYELID DEVELOPMENT AND FEMALE REPRODUCTION
ACTIVIN/INHIBIN BETA-B SUBUNIT GENE DISRUPTION LEADS TO DEFECTS IN EYELID DEVELOPMENT AND FEMALE REPRODUCTION
复制标题
DOI：
10.1101/gad.8.4.414
复制
发表时间：
1994-02-15
影响因子：
10.5
通讯作者：
JAENISCH, R
中科院分区：
文献类型：
--
作者：
VASSALLI, A;MATZUK, MM;JAENISCH, R
抑制素和激活素是转化生长因子-β超家族的二聚体生长因子，转化生长因子-β超家族是一类可以调节多种细胞类型生长和分化的肽。最近，激活素通过其在非洲爪蟾胚胎外植体中诱发中胚层诱导的形态和分子变化特征的能力而与早期脊椎动物发育有关。为了进一步了解这些过程，我们在胚胎干细胞中使用同源重组来创建在编码激活素/抑制素βB亚基的基因中携带突变的小鼠品系。这些小鼠预计缺乏激活素 B（β B：β B）、激活素 AB（β A：β B）和抑制素 B（α：β B）。产生了可存活的突变动物，表明 β B 亚基对于小鼠中胚层的形成并不是必需的。然而，突变动物患有明显的发育和生殖缺陷。胚胎发育后期眼睑融合的明显失败导致突变动物的眼部病变。缺乏βB的雄性可以正常繁殖，而突变的雌性则表现出生殖能力严重受损，其特点是其后代在围产期死亡。突变小鼠的表型表明，激活素 β B (1) 在胎儿晚期发育中发挥作用，并且 (2) 对雌性生育力至关重要。此外，我们发现突变雌性卵巢中激活素相关βA亚基的表达高度上调。 β B 缺陷小鼠中 β A 激活素调节的改变可能导致突变表型。
Inhibins and activins are dimeric growth factors of the transforming growth factor-beta superfamily, a class of peptides that can regulate the growth and differentiation of a variety of cell types. Recently, activins have been implicated in early vertebrate development through their ability to evoke, in Xenopus embryo explants, both morphological and molecular changes characteristic of mesoderm induction. To understand these processes further, we have used homologous recombination in embryonic stem cells to create mouse strains carrying mutations in the gene encoding the activin/inhibin beta B subunit. These mice are expected to be deficient in activin B (beta B:beta B), activin AB (beta A:beta B), and inhibin B (alpha:beta B). Viable mutant animals were generated, indicating that the beta B subunit is not essential for mesoderm formation in the mouse. Mutant animals suffered, however, from distinct developmental and reproductive defects. An apparent failure of eyelid fusion during late embryonic development led to eye lesions in mutant animals. Whereas beta B-deficient males bred normally, mutant females manifested a profoundly impaired reproductive ability, characterized by perinatal lethality of their offspring. The phenotype of mutant mice suggests that activin beta B (1) plays a role in late fetal development and (2) is critical for female fecundity. In addition, we have found that expression of the related beta A subunit of activin is highly upregulated in ovaries of mutant females. Altered regulation of beta A activin in beta B-deficient mice may contribute to the mutant phenotype.