Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure
Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure
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DOI：
10.1186/1471-2156-2-18
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发表时间：
2001-01-01
期刊：
影响因子：
2.9
通讯作者：
John, Simon W. M.
中科院分区：
文献类型：
--
作者：
Chang, Bo;Smith, Richard S.;John, Simon W. M.
背景：青光眼是一种致盲性疾病，通常与高眼压有关。在某些家族中，异常的眼前节发育会导致青光眼。在这些家族中，引起眼前节发育不全和青光眼的基因大多数没有被确定，受影响的发育过程也知之甚少。骨形态发生蛋白（BMP）参与各种发育过程。结果：Bmp 4（+/-）小鼠存在眼前节异常，包括小梁网和Schlemm管引流结构的畸形、缺失或阻塞。具有超过其角范围的80%或更多的严重引流结构异常的小鼠具有升高的IOP。遗传背景强烈影响异常的发生率和严重程度，在C57 BL/6 J背景中最严重，而在其他一些背景中不存在。在C57 BL/6 J背景下，还存在玻璃体血管系统的持续存在、视网膜内细胞数量减少以及视神经的缺失。结论：我们证明BMP 4的杂合缺陷会导致眼前段发育不全和IOP升高。这些异常与患有发育性青光眼的人类患者的异常相似。因此，BMP 4是促成Axenetri-Rieger异常和与人青光眼相关的其他发育状况的强有力的候选者。BMP 4也参与后段发育，野生型水平通常对C57 BL/6 J背景下的视神经发育至关重要。BMP（4+/-）小鼠可用于研究眼发育的各种组分，并且可允许鉴定影响各种眼表型的品系特异性修饰剂。
Background: Glaucoma is a blinding disease usually associated with high intraocular pressure (IOP). In some families, abnormal anterior segment development contributes to glaucoma. The genes causing anterior segment dysgenesis and glaucoma in most of these families are not identified and the affected developmental processes are poorly understood. Bone morphogenetic proteins (BMPs) participate in various developmental processes. We tested the importance of Bmp4 gene dosage for ocular development and developmental glaucoma.Results: Bmp4(+/-) mice have anterior segment abnormalities including malformed, absent or blocked trabecular meshwork and Schlemm's canal drainage structures. Mice with severe drainage structure abnormalities over 80% or more of their angle's extent have elevated IOP. The penetrance and severity of abnormalities is strongly influenced by genetic background, being most severe on the C57BL/6J background and absent on some other backgrounds. On the C57BL/6J background there is also persistence of the hyaloid vasculature, diminished numbers of inner retinal cells, and absence of the optic nerve.Conclusions: We demonstrate that heterozygous deficiency of BMP4 results in anterior segment dysgenesis and elevated IOP. The abnormalities are similar to those in human patients with developmental glaucoma. Thus, BMP4 is a strong candidate to contribute to Axenfeld-Rieger anomaly and other developmental conditions associated with human glaucoma. BMP4 also participates in posterior segment development and wild-type levels are usually critical for optic nerve development on the C57BL/6J background. Bmp(4+/-) mice are useful for studying various components of ocular development, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes.