Wnt5a基因敲除小鼠作为一种肛门直肠畸形的新模型。
Wnt5a knock-out mouse as a new model of anorectal malformation.
作者信息
Tai Cindy C, Sala Frederic G, Ford Henri R, Wang Kasper S, Li Changgong, Minoo Parviz, Grikscheit Tracy C, Bellusci Saverio
机构信息
Division of Pediatric Surgery, Childrens Hospital Los Angeles, Los Angeles, California 90027, USA.
出版信息
J Surg Res. 2009 Oct;156(2):278-82. doi: 10.1016/j.jss.2009.03.087. Epub 2009 May 8.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
背景
肛门直肠畸形（ARM）代表了一系列涉及肛门直肠异常终止的先天性疾病。Shh信号通路和Fgf10中的突变会产生多种ARM表型。Wnt信号通路已被证明在胃肠道发育过程中至关重要。因此，我们推测Wnt5a可能在肛门直肠发育中发挥作用。
方法
从E15.5至E18.5的定时怀孕小鼠中收集野生型（WT）、Wnt5a(+/-)和Wnt5a(-/-)胚胎，并分析其肛门直肠表型。对组织进行全胚原位杂交和组织学处理。
结果
Wnt5a在胚胎期野生型结肠和直肠中表达。Wnt5a(-/-)突变体表现出多种畸形，包括肛门直肠畸形。早在E15.5时就可发现泌尿生殖道与肠道之间存在瘘管。到E18.5时，大多数Wnt5a(-/-)突变体的远端肠道呈现盲端囊袋。
结论
Wnt5a的表达模式以及在Wnt5a(-/-)突变体中观察到的ARM表型证明了Wnt5a在肛门直肠发育过程中的关键作用。本研究建立了一种涉及Wnt5a通路的ARM新模型。
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