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小鼠骨形态发生蛋白II型受体基因的floxed等位基因的产生。

Generation of a floxed allele of the mouse BMP type II receptor gene.

作者信息

Beppu Hideyuki, Lei Hong, Bloch Kenneth D, Li En

机构信息

Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.

出版信息

Genesis. 2005 Mar;41(3):133-7. doi: 10.1002/gene.20099.

Abstract

Bone morphogenetic proteins (BMPs) regulate a wide range of cellular functions that contribute to embryonic development from mesoderm formation to organogenesis. BMP type II receptor (BMPR-II) transduces BMP signals by forming heteromeric complexes with and phosphorylating BMP type I receptors. Heterozygous germline mutations of BMPR-II gene have been identified in patients with familial and sporadic primary pulmonary hypertension, indicating that BMPR-II may contribute to the maintenance of normal pulmonary vascular structure and function. Since embryos homozygous for a null BMPR-II allele died during gastrulation, precluding further studies of BMPR-II function in organ formation and in adult tissues, we generated mice carrying a conditional mutant BMPR-II allele in which exons 4 and 5 were flanked by loxP sequences. We anticipate that studies of mice carrying a floxed BMPR-II allele and a Cre transgene (under the control of a tissue-specific promoter) will enable characterization of the role of BMPR-II in specific cell types during development and in the pathogenesis of cardiovascular diseases.

摘要

骨形态发生蛋白(BMPs)调节多种细胞功能,这些功能有助于胚胎从形成中胚层到器官发生的发育过程。II型骨形态发生蛋白受体(BMPR-II)通过与I型骨形态发生蛋白受体形成异源复合物并使其磷酸化来转导BMP信号。在家族性和散发性原发性肺动脉高压患者中已鉴定出BMPR-II基因的杂合种系突变,这表明BMPR-II可能有助于维持正常的肺血管结构和功能。由于纯合缺失BMPR-II等位基因的胚胎在原肠胚形成期间死亡,从而无法进一步研究BMPR-II在器官形成和成年组织中的功能,因此我们构建了携带条件性突变BMPR-II等位基因的小鼠,其中第4和第5外显子两侧为loxP序列。我们预计,对携带floxed BMPR-II等位基因和Cre转基因(在组织特异性启动子的控制下)的小鼠进行研究,将能够阐明BMPR-II在发育过程中特定细胞类型以及心血管疾病发病机制中的作用。

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