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¹ Department of Pharmacology and ² Horizontal Medical Research Organization, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606-8501, Japan
³ Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan
⁴ Department of Obstetrics and Gynecology, Shiga University of Medical Science, Ohtsu, Shiga 520-2191, Japan

Rho-associated kinase (ROCK) is a serine/threonine kinase working in the Rho signaling to actin cytoskeleton. We previously reported that loss of ROCK-I results in the eyelid open at birth (EOB) and omphalocele phenotype in mice, while loss of ROCK-II results in placental dysfunction leading to intrauterine growth retardation and fetal death. Here, we report that after backcross to the C57BL/6 N genetic background, ROCK-II knockout (KO) neonates are born also with open eyelid and umbilical hernia, a phenotype similar to that of ROCK-I KO mice. ROCK-II KO embryos show impaired extension of the eyelid epithelial sheet with disorganized actin bundles in the leading edge of the sheet. These results suggest that ROCK-I and ROCK-II cooperatively regulates the assembly of actin bundles essential for closure of the eyelid and ventral body wall in mouse embryos. Consistently, ROCK-I^+/–ROCK-II^+/– double heterozygous mice also show the EOB and omphalocele phenotype.

^* Correspondence: E-mail: snaru{at}mfour.med.kyoto-u.ac.jp

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