Beppu Hideyuki, Lei Hong, Bloch Kenneth D, Li En
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Genesis. 2005 Mar;41(3):133-7. doi: 10.1002/gene.20099.
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.
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。