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M. Mao, M. Anderson; A New Mouse Model of Early Onset Glaucoma Caused by Sh3pxd2b. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2151.
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Mouse models of glaucoma are valuable resources for studying the molecular basis of glaucoma susceptibility. A spontaneously derived mouse mutant, nee, which contains a 1 bp deletion in Sh3pxd2b, was recently shown to exhibit ocular defects suggestive of glaucoma. Here, we present a detailed phenotypic characterization of nee mutants and expression analysis of SH3PXD2B to closely examine the potential contributions of Sh3pxd2b to glaucoma pathology.
In the anterior segment, slit-lamp examination showed that nee homozygotes exhibit peripheral anterior synechia starting at P17. Increased anterior chamber depth and elevated IOP was observed in mice over one month of age. In the posterior segment, P17 nee homozygotes initially exhibit a normal retina. Cross sections of the optic nerves of P17 nee homozygotes showed a normal morphology; however, the number of myelinated axons is slightly less than wild-type littermates (nee = 20988 +/- 2183, n = 10; homozygous wild-type = 25860 +/- 3656, n = 13; p< 0.05). Consistent with a glaucomatous pathology, nee mutants rapidly developed optic nerve head excavation and axon loss. By 3 months of age, nee homozygotes had a severe degeneration of the ganglion cell layer and optic nerve. To further determine the mechanisms through which SH3PXD2B might contribute to glaucoma, we examined its expression in human tissue, finding that SH3PXD2B is wildly expressed in the eye, including the trabecular meshwork and retina.
We have identified a new mouse model which exhibits phenotypes resembling a form of early onset glaucoma. Because of its early age of onset, nee mutant mice represent a valuable resource for mechanistic studies of glaucoma that does not require expensive aging of mice. SH3PXD2B is also suggested to influence function of the trabecular meshwork and as a candidate potentially contributing to human glaucoma.
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