He Zhi-Yong, Brakebusch Cord, Fässler Reinhard, Kreidberg Jordan A, Primakoff Paul, Myles Diana G
Section of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, USA.
Dev Biol. 2003 Feb 15;254(2):226-37. doi: 10.1016/s0012-1606(02)00043-x.
Antibody inhibition and alpha6beta1 ligand binding experiments indicate that the egg integrin alpha6beta1 functions as a receptor for sperm during gamete fusion; yet, eggs null for the alpha6 integrin exhibit normal fertilization. Alternative integrins may be involved in sperm-egg binding and fusion and could compensate for the absence of alpha6beta1. Various beta1 integrins and alphav integrins are present on mouse eggs. Some of these integrins are also reported to be receptors for ADAMs, which are expressed on sperm. Using alpha3 integrin null eggs, we found that the alpha3beta1 integrin was not essential for sperm-egg binding and fusion. Oocyte-specific, beta1 integrin conditional knockout mice allowed us to obtain mature eggs lacking all beta1 integrins. We found that the beta1 integrin null eggs were fully functional in fertilization both in vivo and in vitro. Furthermore, neither anti-mouse beta3 integrin function-blocking monoclonal antibody (mAb) nor alphav integrin function-blocking mAb inhibited sperm binding to or fusion with beta1 integrin null eggs. Thus, function of beta3 or alphav integrins does not seem to be involved in compensating for the absence of beta1 integrins. These results indicate that none of the integrins known to be present on mouse eggs or to be ADAM receptors are essential for sperm-egg binding/fusion, and thus, egg integrins may not play the role in gamete fusion previously attributed to them.
抗体抑制和α6β1配体结合实验表明,卵子整合素α6β1在配子融合过程中作为精子的受体发挥作用;然而,α6整合素缺失的卵子受精情况正常。其他整合素可能参与精卵结合与融合,并可弥补α6β1缺失的影响。小鼠卵子上存在多种β1整合素和αv整合素。据报道,其中一些整合素也是ADAMs的受体,ADAMs在精子上表达。利用α3整合素缺失的卵子,我们发现α3β1整合素对精卵结合与融合并非必不可少。卵母细胞特异性β1整合素条件性敲除小鼠使我们能够获得缺乏所有β1整合素的成熟卵子。我们发现β1整合素缺失的卵子在体内和体外受精中均功能完全正常。此外,抗小鼠β3整合素功能阻断单克隆抗体(mAb)和αv整合素功能阻断mAb均未抑制精子与β1整合素缺失卵子的结合或融合。因此,β3或αv整合素的功能似乎不参与弥补β1整合素缺失的影响。这些结果表明,已知存在于小鼠卵子上或作为ADAM受体的整合素,均对精卵结合/融合并非必不可少,因此,卵子整合素可能并不发挥先前认为的在配子融合中的作用。