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Yang Liu, Matthew Warman, David A Sullivan, Steven Hann, Di Chen; Ocular manifestations of chordin-like 1 (Chrdl1) knockout mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4150.
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© ARVO (1962-2015); The Authors (2016-present)
In humans, loss-of-function mutations in the gene encoding Chordin-like 1 (CHRDL1) cause X-linked megalocornea (MGC1), a congenital disorder predominantly affecting males, that is characterized by bilateral corneal enlargement, central corneal mosaic dystrophy, increased anterior chamber depth, shortened vitreous length and normal intraocular pressure. We sought to determine whether Chrdl1 knockout (KO) mice would recapitulate the ocular findings found in patients with MGC1.
We obtained an embryonic stem cell line in which the first coding exon of Chrdl1 was deleted by homologous recombination from Lexicon Pharmaceuticals, and used this cell line to generate mice. Female mice heterozygous for the Chrdl1 KO allele were crossed with wild-type (WT) males. Male offspring from this cross that were WT (N=7) or KO (N=8) were analyzed when 8.7 ± 0.6 and 5.5 ± 0.8 months old, respectively.Corneal diameter, area, thickness, fluorescein staining and endothelial cell density, anterior chamber depth, tear volume, and conscious intraocular pressure were measured. Animals were then euthanized and retinas were harvested and processed to count retinal ganglion cell number.
The only differences we observed between KO and WT mice were in central corneal thickness, which was larger, and anterior chamber depth, which was smaller, in the KO mice. Otherwise, KO mice did not differ from WT in corneal diameter, area, fluorescein staining and endothelial cell density, anterior chamber depth, tear volume, conscious intraocular pressure, and retinal ganglion cell number.
Male Chrdl1 KO mice do not have the ocular findings that occur in patients with MGC1. Although KO mice differ from WT littermates with respect to central corneal thickness and anterior chamber depth, these differences are opposite to those that occur in humans. Therefore, with regard to corneal and ocular structure, Chrdl1 KO mice are not useful for modeling MGC1.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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