Conditional deletion of AP-2β in mouse cranial neural crest results in anterior segment dysgenesis and early-onset glaucoma.
Conditional deletion of AP-2β in mouse cranial neural crest results in anterior segment dysgenesis and early-onset glaucoma.
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DOI：
10.1242/dmm.025262
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发表时间：
2016-08-01
影响因子：
4.3
通讯作者：
West-Mays JA
中科院分区：
文献类型：
--
作者：
Martino VB;Sabljic T;Deschamps P;Green RM;Akula M;Peacock E;Ball A;Williams T;West-Mays JA
前段发育不良（ASD）包括一组发育障碍，其中眼睛前房可发生闭角表型，50%的患者发展为青光眼。许多自闭症被认为与眼周间质（POM）的不适当模式和迁移有关，POM来源于颅神经嵴细胞（NCCs）和中胚层。虽然这种破坏的机制尚不清楚，但许多转录调节分子先前与自闭症有关。在这里，我们研究了转录因子AP-2β的功能，该转录因子由Tfap2b编码，在ncc及其衍生物中表达。NCCs中wnt1 - cre介导的Tfap2b条件缺失导致以不透明为特征的出生后眼部缺陷。组织学数据显示，条件AP-2β NCC敲除（KO）突变体在眼前段表现出多种结构的发育不良，包括角膜内皮、角膜基质、睫状体的缺陷和虹膜-角膜角的破坏，虹膜与角膜的粘附。我们进一步表明，这种表型导致眼压显著升高，随后视网膜神经节细胞丢失和视神经变性，这是青光眼的特征。总的来说，我们的研究结果表明，AP-2β在POM中是眼睛前段正常发育所必需的，并且AP-2β NCC KO小鼠可能作为一种新的令人兴奋的ASD和青光眼模型，具有完全渗透性和产后早期发病。摘要：神经嵴源性眼周间质中转录因子AP-2β的组织特异性缺失产生了小鼠前段发育不良和早发性青光眼的新模型。
Anterior segment dysgenesis (ASD) encompasses a group of developmental disorders in which a closed angle phenotype in the anterior chamber of the eye can occur and 50% of patients develop glaucoma. Many ASDs are thought to involve an inappropriate patterning and migration of the periocular mesenchyme (POM), which is derived from cranial neural crest cells (NCCs) and mesoderm. Although, the mechanism of this disruption is not well understood, a number of transcriptional regulatory molecules have previously been implicated in ASDs. Here, we investigate the function of the transcription factor AP-2β, encoded by Tfap2b, which is expressed in NCCs and their derivatives. Wnt1-Cre-mediated conditional deletion of Tfap2b in NCCs resulted in post-natal ocular defects typified by opacity. Histological data revealed that the conditional AP-2β NCC knockout (KO) mutants exhibited dysgenesis of multiple structures in the anterior segment of the eye including defects in the corneal endothelium, corneal stroma, ciliary body and disruption in the iridocorneal angle with adherence of the iris to the cornea. We further show that this phenotype leads to a significant increase in intraocular pressure and a subsequent loss of retinal ganglion cells and optic nerve degeneration, features indicative of glaucoma. Overall, our findings demonstrate that AP-2β is required in the POM for normal development of the anterior segment of the eye and that the AP-2β NCC KO mice might serve as a new and exciting model of ASD and glaucoma that is fully penetrant and with early post-natal onset. Summary: Tissue-specific deletion of transcription factor AP-2β in the neural-crest-derived periocular mesenchyme generates a novel model of anterior segment dysgenesis and early onset glaucoma in mice.
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影响因子：
3.6
作者：
Jin K;Jiang H;Xiao D;Zou M;Zhu J;Xiang M
通讯作者：
Xiang M
影响因子：
2.5
作者：
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影响因子：
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作者：
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Masland, Richard H
影响因子：
4.4
作者：
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通讯作者：
Weinreb, RN
影响因子：
2
作者：
Kipfer-Kauer A;McKinnon SJ;Frueh BE;Goldblum D
通讯作者：
Goldblum D