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N. L. Hawes, M. Mao, B. Chang, P. Fuerst, R. S. Smith, S. W. M. John, J. R. Heckenlively, M. G. Anderson, L. Donahue; Sh3pxd2b Mutation Causes Anterior Segment Dysgenesis in Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5109. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
In order to facilitate better understanding of the developmental events contributing to anterior segment dysgenesis (ASD), we have been screening for new mouse models exhibiting ASD-related phenotypes. Here, we report an initial phenotypic and genetic characterization of the spontaneously arising nee mutation, a new mouse model involving ASD, craniofacial abnormalities, and retinal ganglion cell loss.
The nee mutation spontaneously arose at The Jackson Laboratory in the strain B10.A-H2(h4)(4R)/SgDvEg. Ocular effects of the nee mutation were documented using slit-lamp exams, fundus photography, electroretinography, and histology. Genetic analysis was performed using linkage studies and molecular analysis.
Mice carrying the nee mutation were initially identified by the presence of its most striking external consequences; homozygous nee mutants are runts with craniofacial abnormalities characterized by small heads, bupthalmic eyes, and flattened noses. Slit-lamp examination shows that homozygotes typically exhibit age related corneal damage, cataracts, and anterior synechias. In order to determine whether these anterior defects might also be associated with glaucoma, we next examined the retina of nee mutant mice. Consistent with glaucoma, the nee mutant mouse retina exhibits excavation of the optic nerve by indirect ophthalmoscopy and histologic examination shows loss of ganglion and inner nuclear layers. However, these analyses have also detected a number of additional phenotypes perhaps indicating a complex pathophysiology, including optic nerve colobomas and retinal vessel abnormalities. Genetic analysis shows that nee is an autosomal recessive mutation that maps to mouse chromosome 11 and caused by a one base pair deletion in Sh3pxd2b.
We have isolated a new mouse model exhibiting ASD like phenotypes and demonstrated that the phenotypes of these mice are caused by a mutation in the Sh3pxd2b gene. Sh3pxd2b is a relatively unstudied gene that is predicted to encode an adapter protein likely to play a role in regulating the localization of binding partners to the plasma membrane. Our future studies will continue to study the role of this gene in ocular development, and further refine the extent to which nee mutant mice may serve as model of early onset glaucoma.
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