Targeting of endothelin receptor-B to the neural crest.

Targeting of endothelin receptor-B to the neural crest.
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DOI:
10.1002/dvg.20415
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发表时间:
2008-08
期刊:
影响因子:
1.5
通讯作者:
Epstein, Miles L.
Epstein, Miles L.
中科院分区:
生物学4区
文献类型:
--
作者:
Druckenbrod, Noah R.;Powers, Patricia A.;Bartley, Christopher R.;Walker, Jeffery W.;Epstein, Miles L.

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内皮素受体B(Ednr B)在肠神经系统的黑素细胞、神经元和神经胶质的发育中起关键作用。这些不同的神经嵴来源的细胞类型表达Ednrb,并具有插入组织的特性,例如肠,其肌肉前体细胞也表达Ednrb。这种广泛的Ednrb表达一直是建立Ednrb在发育中的精确作用的重大障碍。我们在这里描述的生产Ednrb等位基因floxed在外显子3和它的使用在切除受体从小鼠神经嵴细胞通过使用Cre重组酶驱动的Wnt1启动子。出生时具有神经嵴特异性Ednrb切除的小鼠具有无神经节结肠,缺乏躯干色素沉着,并在五周内因巨结肠而死亡。在这些动物中,Ednrb受体表达仅在神经嵴中不存在,但存在于周围的平滑肌细胞中。嵴细胞中Ednrb的缺失也导致肠内其他细胞中Ednrb表达的补偿性上调。我们的结论是,Ednrb损失仅在神经嵴细胞是足以产生的Hirschsprungs病的表型观察基因组Ednrb突变。
Endothelin receptor B (Ednrb) plays a critical role in the development of melanocytes and neurons and glia of the enteric nervous system. These distinct neural crest-derived cell types express Ednrb and share the property of intercalating into tissues, such as the intestine whose muscle precursor cells also express Ednrb. Such widespread Ednrb expression has been a significant obstacle in establishing precise roles for Ednrb in development. We describe here the production of an Ednrb allele floxed at exon 3 and its use in excising the receptor from mouse neural crest cells by use of Cre-recombinase driven by the Wnt1 promoter. Mice born with neural crest-specific excision of Ednrb possess aganglionic colon, lack trunk pigmentation, and die within five weeks due to megacolon. Ednrb receptor expression in these animals is absent only in the neural crest but present in surrounding smooth muscle cells. The absence of Ednrb from crest cells also results in a compensatory upregulation of Ednrb expression in other cells within the gut. We conclude that Ednrb loss only in neural crest cells is sufficient to produce the Hirschsprungs disease phenotype observed with genomic Ednrb mutations.
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