Wnt5a knock-out mouse as a new model of anorectal malformation.
Wnt5a knock-out mouse as a new model of anorectal malformation.
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Wnt5a敲除鼠标是一种新的肛门直肠畸形模型。
DOI：
10.1016/j.jss.2009.03.087
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Bellusci S
中科院分区：
文献类型：
--
作者：
Tai CC;Sala FG;Ford HR;Wang KS;Li C;Minoo P;Grikscheit TC;Bellusci S
肛门直肠畸形（ARM）代表了各种先天性疾病，涉及异常终止肛门直肠。Shh信号和Fgf 10的突变产生多种ARM表型。Wnt信号已被证明在胃肠道发育过程中至关重要。因此，我们假设Wnt 5a可能在肛门直肠发育中发挥作用。从E15.5至E18.5的定时妊娠小鼠中收获野生型（WT）、Wnt 5a +/-和Wnt 5a-/-胚胎，并分析肛门直肠表型。处理组织进行整体原位杂交和组织学检查。Wnt 5a在胚胎WT结肠和直肠中表达。Wnt 5a-/-突变体表现出多种畸形，包括肛门直肠畸形。早在E15.5就可以发现泌尿道和肠道之间的瘘管。到E18.5，大多数Wnt 5a-/-突变体显示出远端肠的盲端袋。Wnt 5a的表达模式和Wnt 5a-/-突变体中观察到的ARM表型证明了Wnt 5a在肛门直肠发育过程中的关键作用。本研究建立了一个新的涉及Wnt 5a通路的ARM模型。
Anorectal malformations (ARM) represent a variety of congenital disorders that involve abnormal termination of the anorectum. Mutations in Shh signaling and Fgf10 produce a variety of ARM phenotypes. Wnt signaling has been shown to be crucial during gastrointestinal development. We therefore hypothesized that Wnt5a may play a role in anorectal development. Wild type (WT), Wnt5a+/-, and Wnt5a-/- embryos were harvested from timed pregnant mice from E15.5 to E18.5 and analyzed for anorectal phenotype. Tissues were processed for whole-mount in situ hybridization and histology. Wnt5a is expressed in the embryonic WT colon and rectum. Wnt5a-/- mutants exhibit multiple deformities including anorectal malformation. A fistula between the urinary and intestinal tracts can be identified as early as E15.5. By E18.5, the majority of the Wnt5a-/- mutants display a blind-ending pouch of the distal gut. The expression pattern of Wnt5a and the ARM phenotype seen in Wnt5a-/- mutants demonstrate the critical role of Wnt5a during anorectal development. This study establishes a new model of ARM involving the Wnt5a pathway.
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