骨形态发生蛋白对鼠小脑浦肯野细胞发育的重要性  

Importance of bone morphogenetic protein in development of cerebellar Purkinje cells of mice

作　　者：秦丽华[1] E. Bryan Crenshaw Ⅲ 雷季良[1] 周长满[1] 

机构地区：[1]北京大学医学部解剖学与组织胚胎学系,北京市100083 [2]费城儿童医院耳鼻喉科儿童感染中心神经遗传学组

出　　处：《中国临床康复》2006年第26期92-94,i0002,共4页Chinese Journal of Clinical Rehabilitation

摘　　要：目的:观察骨形态发生蛋白通过Ⅰ型受体传导信号在小脑浦肯野细胞发育中的作用。为揭示临床有关骨形态发生蛋白引起的遗传病发病及治疗提供有力的依据。方法:实验于2004-03/2005-08在美国费城儿童医院Crenshaw实验室和北京大学医学部解剖学神经研究实验室完成。小鼠种类为C57Bl/6J,敲除了骨形态发生蛋白Ⅰ型受体的Bmpr1a和Bmpr1b两个亚型基因,产生了条件性的BMPR-ⅠA和经典性的BMPR-ⅠB受体敲除鼠,破坏了在小脑内的骨形态发生蛋白信号转导。并使用免疫双标calbindin,Tuj1估计小鼠胚胎13.5d和新生幼鼠的浦肯野细胞发育分化情况。结果:①在小鼠刚出生时,正常组鼠的浦肯野细胞都迁移到了小脑,并形成浦肯野细胞层;但在Bmpr1a/Bmpr1b双敲除鼠的浦肯野细胞迁移明显异常,大部分Calbindin阳性的浦肯野细胞呈簇状位于小脑深部,另有部分细胞迁移到了中脑下丘。②免疫双标显示在正常组双标的细胞位于小脑的腹侧缘;但在Bmpr1a/Bmpr1b双敲除组,双标记的浦肯野细胞数量明显减少,并且浦肯野细胞排列紊乱,说明浦肯野细胞的分化受到影响。结论:①骨形态发生蛋白信号对浦肯野细胞的作用可能不是直接的,或许是经过一些中间环节来完成的。②只有两受体基因Bmpr1a和Bm-pr1b同时敲除才能影响骨形态发生蛋白信号对小脑浦肯野细胞发育的作用。AIM： To observe the effect of bone morphogenetic protein （BMP） signaling through BMP receptor type Ⅰ （BMPR- Ⅰ ） on the development of cerebellar Purkinje cells, and provide powerful evidence for revealing the pathogenesis and treatment of some hereditary diseases caused by the dysfunction of BMP. METHODS： The experiment was conducted at the Crenshaw Laboratory of The Children＇s Hospital of Philadelphia and at the Laboratory of Anatomy and Neurological Research, Peking University Health Science Center between March 2004 and August 2005. Mice of C57B1/6J species were selected to knock out two subtype gene Bmprla and Bmprlb of BMPR- Ⅰ and generate the conditional knockout of the gene encoding BMPR- ⅠA and null knockout of BMPR- Ⅰ B mutants that disrupted BMP signal transduction in the cerebellum. The development and differentiation of Purkinje cells were detected with double immunostaining labeled by calbindin and Tujl in mouse embryo of 13.5 days old and neonatal mice. RESULTS： ①Purkinje cells migrated into cerebellum and formed a layer in normal newly-born mice; The migrations of Purkinje cells were found obviously abnormal in Bmprla/Bmprlb knockout mice. Most of Calbindinpositive Purkinje cells were located clusterly in the deep cerebellum. Some cells migrated into inferior colliculus of midbrain.②Double immunostainlng cells were found at the ventral side of normal cerebellum; But the number of double immunostaining cells was obviously decreased and disorganized in Bmprla/Bmprlb knockout mice, which indicated that the differentiation of Purkinje cells were affected. CONCLUSION： ①The signaling via BMPR- Ⅰ plays a direct or indirect important role in the differentiation and migration of Purkinje cells in genetics.②BMP is effective for the development of cerebellar Purkinje cells only when both Bmprla and Bmprlb receptors are knocked out simultaneously.

关 键 词：骨形态发生蛋白质类 小鼠 基因敲除 浦肯野细胞 

分 类 号：R596[医药卫生—内科学]