title: Impaired vascular remodeling in the yolk sac of embryos deficient in ROCK-I and ROCK-II.
abstract: 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.
authors: Department of Pharmacology, Kyoto University, Japan.
authors: Hiroshi
authors: H
authors: Kamijo
authors: Yutaka
authors: Y
authors: Matsumura
authors: Dean
authors: D
authors: Thumkeo
authors: Seiichi
authors: S
authors: Koike
authors: Masayuki
authors: M
authors: Masu
authors: Yoshihiko
authors: Y
authors: Shimizu
authors: Toshimasa
authors: T
authors: Ishizaki
authors: Shuh
authors: S
authors: Narumiya
mesh_terms: D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000235:genetics; D010641:Phenotype; D015017:Yolk Sac / Q000098:blood supply* / Q000201:enzymology*; D054460:rho-Associated Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D054460:rho-Associated Kinases