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BMC Genetics 2001
Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressureAbstract: 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.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. Bmp4+/- mice are useful for studying various components of ocular development, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes.Glaucoma is a leading cause of blindness that involves loss of retinal ganglion cells and degeneration of the optic nerve [1]. Glaucoma is usually associated with high intraocular pressure (IOP) that results from an increased resistance to drainage of the ocular fluid [1]. Developmental disorders of the ocular anterior segment, including Axenfeld-Rieger syndrome, are often associated with elevated IOP and glaucoma [1,2]. The developmental sequence and structure of the human and mouse ocular drainage structures are similar [3], and the same genes are known to cause anterior segment dysgenesis (ASD) in humans and mice. Known genes that cause anterior segment dysgenesis code for developmentally important transcription factors. These ge
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