Department of Pharmacology, Kyoto University, Japan.
Genes Cells. 2011 Oct;16(10):1012-21. doi: 10.1111/j.1365-2443.2011.01546.x. Epub 2011 Sep 5.
Rho-associated coiled-coil-forming protein serine/threonine kinase (ROCK) consisting of two isoforms, ROCK-I and ROCK-II, functions downstream of the small GTPase Rho for assembly of actomyosin bundles. To examine the role of ROCK isoforms in vivo, we previously generated and examined mice deficient in each of the two isoforms individually. Here, we further examined the in vivo role of ROCK isoforms by generating mice deficient in both isoforms. Cross-mating of ROCK-I(+/-) ROCK-II(+/-) double heterozygous mice showed that all of the ROCK-I(-/-) ROCK-II(-/-) homozygous mice die in utero before 9.5 days post-coitum (dpc) and ROCK-I(-/-) ROCK-II(+/-) homo-heterozygous or ROCK-I(+/-) ROCK-II(-/-) hetero-homozygous mice die during a period from 9.5 to 12.5 dpc, whereas mice of other genotypes survive until 12.5 dpc with the expected Mendelian ratio. All of the ROCK-I(+/-) ROCK-II(-/-) or ROCK-I(-/-) ROCK-II(+/-) mice showed impaired body turning and defective vascular remodeling in the yolk sac. Impairment of vascular remodeling was also observed in wild-type embryos treated ex vivo with a ROCK inhibitor, Y-27632. These results suggest that ROCK isoforms function redundantly during embryogenesis and play a critical role in vascular development.
Rho 相关卷曲螺旋形成蛋白丝氨酸/苏氨酸激酶（ROCK）由两个同工型组成，ROCK-I 和 ROCK-II，作为小 GTP 酶 Rho 的下游因子，其功能是肌动球蛋白束的组装。为了在体内研究 ROCK 同工型的作用，我们之前分别生成并检查了两种同工型缺陷的小鼠。在这里，我们通过生成两种同工型都缺陷的小鼠进一步研究了 ROCK 同工型在体内的作用。ROCK-I(+/-) ROCK-II(+/-)双杂合子小鼠的交叉交配表明，所有 ROCK-I(-/-) ROCK-II(-/-)纯合子小鼠都在胚胎受精后 9.5 天内死于子宫内，而 ROCK-I(-/-) ROCK-II(+/-)同型纯合子或 ROCK-I(+/-) ROCK-II(-/-)异型纯合子小鼠则在 9.5 至 12.5 天的期间死亡，而其他基因型的小鼠则以预期的孟德尔比例存活到 12.5 天。所有 ROCK-I(+/-) ROCK-II(-/-)或 ROCK-I(-/-) ROCK-II(+/-)小鼠都表现出身体转动受损和卵黄囊血管重塑缺陷。在 ROCK 抑制剂 Y-27632 处理的野生型胚胎中也观察到血管重塑受损。这些结果表明，ROCK 同工型在胚胎发生过程中具有冗余功能，并在血管发育中发挥关键作用。
