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  • 庄涛,张清泉,孙云甫.Isll在后肢发育过程中的表达及作用[J].同济大学学报(医学版),2013,34(5):1-6.    [点击复制]
  • ZHUANG Tao,ZHANG Qing-quan,SUN Yun-fu.Role of Isll in hindlimb development of mice[J].同济大学学报(医学版),2013,34(5):1-6.   [点击复制]
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Isll在后肢发育过程中的表达及作用
庄涛,张清泉,孙云甫
0
(同济大学医学院,上海200120 ;同济大学附属东方医院医学转化平台,上海200120)
摘要:
目的研究Isll在后肢发育过程中的表达及作用。方法使用Isll—nLacZ、Isll-Cre、HoxB6-Cre和Isllvt小鼠模型,以及X—gal染色、骨染色、组织分析方法研究Isll在后肢发育过程中的表达及作用。结果随着小鼠后肢开始发育,在胚胎期第10.5天,Isll在后肢原基高表达。在胚胎逐渐发育至胚胎期第12.5天的过程中,Isll在后肢的表达逐渐下调。在胚胎期第12.5天,Isll仅在后肢的最后部表达。但在胚胎期第13.5、15.5天,Isll在后肢的后半部表达明显升高,主要在后肢骨骼肌细胞中表达。Isll—Cre谱系研究显示,Isll参与后肢的骨和骨骼肌细胞的形成。利用HoxB6.Cre在后肢中敲除Isll可导致突变鼠后肢发育严重异常,伴有坐骨,耻骨,腓骨和跟骨及脚趾骨发育不良或缺失,突变鼠5号脚趾缺失最多见,而1号脚趾缺失累及较少。突变鼠后肢骨骼肌细胞的中央核比例远高于对照组。结论Isll在小鼠后肢发育过程中动态表达,参与后肢骨骼肌细胞和骨细胞的发育,对后肢发育过程中近一远和前后轴的建立起重要作用。
关键词:  Isll  后肢  骨细胞  骨骼肌细胞  HoxB6-Cre
DOI:10. 3969/j. issnl008 - 0392.2013. 05.001
基金项目:国家自然科学基金(31071280)
Role of Isll in hindlimb development of mice
ZHUANG Tao,ZHANG Qing-quan,SUN Yun-fu
(School of Medicine, Tongji University, Shanghai 200120, China;Translational Medicine Platform of East Hospital, Tongji University, Shanghai 200120, China))
Abstract:
Objective To investigate the expression and role of Isll in mouse hindlimb development. Methods Isll-nLacZ, Isll-Cre, HoxB6-Cre, Isllf/e mice and X-gal staining, bone staining, histological analysis were used to investigate expression and role of Isll during limb development. Results During limb bud development, Isll was expressed highly in hindlimb bud at El0.5. Isll expression in hindlimb was downregluated afterwards. Isll expression wass retained only at the posterior-most edge of the hindlimb at El2.5. At El3.5 and El5.5, Isll expression was increased in the posterior half of the hindlimb. Isll-Cre lineage study demonstrated that Isll-Cre lineage contributed to the formation of skeletal muscle and bone cells in the hindlimb. Ablation of Isll using HoxB6-Cre resulted in severe hindlimb malformation with missing ischium, pubis, fibula, calcaneus and posterior digits. In these mutants, the most posterior digit 5 was alwaysmissing, whereas the most anterior digit 1 appeared normal. Compared to control tlttermates, a large proportion of skeletal muscle cells of mutant embryos exhibited centralized nuclei. Conclusion Isll is expressed in hindlimb dynamically and Isll progenitors contribute to the formation of skeletal muscle and bone ceils. Isll plays essential roles in bone development of the hindlimb. Isll may be involved in hindlimb muscle development.
Key words:  Isll  hindlimb  bone cells  skeletal muscle cells  HoxB6-Cre

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