NULL MUTATIONS OF VERTEBRATE NONMUSCLE MYOSIN HEAVY CHAINS

脊椎动物非肌肉肌球蛋白重链的无效突变

• 批准号: 6109252
• 负责人: ROBERT ADELSTEIN
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6109252
• 关键词: congenital heart disorder; developmental genetics; disease /disorder model; gene deletion mutation; gene targeting; genetic recombination; genetically modified animals; heart cell; laboratory mouse; myosins; phenotype; protein isoforms; retina; vertebrate embryology

Previous work from this laboratory demonstrated that ablation of the nonmuscle myosin II-B heavy chain (NMHC-B) in mice resulted in a cardiac ventricular septal defect and abnormalities of the aortic outflow tract. These B-/B- mice all demonstrated hydrocephalus and died in utero or just after birth (PO). Analysis of brains from E12.5, E13.5 and E15 mice identified developmental defects in the ventricular neuroepithelium. On E12.5, disruption of the cells lining the ventricular surface along with abnormal migration of the neuroepithelial cells was seen in parts of the ventricular wall. Identification of mitotic cells outside of the ventricular surface layer was consistent with an abnormality in interkinetic nuclear migration. On E13.5 and E15, there was a protrusion of cells into the ventricle and on E18.5 and PO, the defects in the ependymal cell layer resulted in stenosis of the cerebal aqueduct or obstruction of the fourth ventricle. Immunofluorescence staining using antibodies to NMHC-B as well as gamma-catenin showed localization of both epitopes to the ventricular surface. These findings raise the possibility that the defects observed in the brain may be related to an alteration in the adhesive properties of the cells.

该实验室的先前工作已证明 非肌肉肌球蛋白II-B重链（NMHC-B）的消融 在小鼠中，导致心室室间隔缺陷和 主动脉流出道的异常。这些b-/b鼠全部 表现出脑积水，死于子宫或出生后 （po）。鉴定出E12.5，E13.5和E15小鼠的大脑的分析 心室神经上皮的发育缺陷。在 E12.5，沿着心室表面内壁的细胞破坏 在神经上皮细胞的异常迁移中被发现 心室壁的一部分。鉴定外面有丝分裂细胞 心室表面层与异常一致 在基础核迁移中。在E13.5和E15上，有一个 细胞向心室和E18.5和PO伸出 室管膜细胞层中的缺陷导致大脑狭窄 第四脑室的渡槽或阻塞。 也使用抗NMHC-B抗体的免疫荧光染色 正如伽马 - 钙蛋白显示出两个表位的定位 心室表面。这些发现增加了 在大脑中观察到的缺陷可能与 细胞的粘附特性。