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M. Z. Karim, N. Comes, L. K. Buie, T. Borras; Characterization of the Eye of the Matrix Gla (MGP) Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3219.
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MGP is highly expressed in chondrocytes and vascular smooth muscle cells. MGP is also one of the ten most abundant genes of the trabecular meshwork (TM). MGP is an inhibitor of calcification and plays a key role in the formation of atherosclerotic plaques and vascular calcification. The MGP knockout (KO) dies between 6-8 weeks of age due to extensive arterial calcification. Our goal was to examine the effect of silencing MGP in the eye in a living animal.
A C57BL/6J male MGP+/- was crossed with C57BL/6J WT females for the generation of heterozygous (HET) of both sexes. Litters from HET breeding pairs were ear-tagged and genotyped by conventional PCR with primers 5’GCC ACA ATT TCT GCA TCC TGC-3’ and 5’-CGG GAA AGA TGA GGA AGA AGGG-3’ using DNA from tail biopsies. Eyes from homozygous (HOMO) and WT littermates were examined for intraocular pressure (IOP), enucleated, fixed with 4% PARA, 2.5 % glutaraldehyde, embedded in Spurr resin and their morphology evaluated for light and electron microscopy (EM).
HOMO mice were identified by the appearance of a 1 kb band in the PCR gels. HOMO mice displayed no phenotypic differences within the first two weeks of life. Thereafter, the mice were shorter than their littermates, had a rapid heartbeat, and died within two months. First measurements indicated that the mice had significantly higher IOP than their littermates WT (13.8 ± 0.28 versus 10.0± 0.24 mmHg). By light microscopy, the morphology of the HOMO’s TM region compared to that of the WT appeared at times thicker, with a not well-formed Schlemm’s canal (SC); the angle looked narrower and often, ciliary process and iris were stuck to the corneal endothelium. By EM, the SC inner-wall cell layer appeared to be discontinuous and often the canal did not close all around. Some HOMO mice, albeit not all, exhibited retina degeneration. All WT had well-developed retinas. Further characterization, including presence of calcification markers, is ongoing.
The MGP gene seems to be needed for the formation of a normal SC in the mouse. Elevated IOP in this KO mouse could be an indication that inhibition of calcification could be important in regulating outflow resistance and IOP.
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