Ocular Manifestations Of Chordin-Like 1 Knockout Mice

Purpose: In humans, loss-of-function mutations in the gene encoding Chordin-like 1 (CHRDL1) cause X-linked megalocornea (MGC1), characterized by bilateral corneal enlargement, decreased corneal thickness, and increased anterior chamber depth (ACD). We sought to determine whetherChrdl1knockout (KO) mice would recapitulate the ocular findings found in patients with MGC1. Methods: We generated mice with aChrdl1KO allele and confirmed that maleChrdl1hemizygous KO mice do not expressChrdl1mRNA. We examined the eyes of male mice that were hemizygous for either the wild-type (WT) or KO allele and measured corneal diameter, corneal area, corneal thickness, endothelial cell density, ACD, tear volume, and intraocular pressure. We also harvested retinas and counted retinal ganglion cell numbers. Eye segregation pattern in the dorsal lateral geniculate nucleus were also compared between maleChrdl1KO and WT mice. Results: MaleChrdl1KO mice do not have larger cornea diameters than WT mice. KO mice have significantly thicker central corneas (116.5 +/- 3.9 vs. 100.9 +/- 4.2 mu m,P= 0.013) and smaller ACD (325.7 +/- 5.7 vs. 405.6 +/- 6.3 mu m,P< 0.001) than WT mice, which is the converse of what occurs in patients who lack CHRDL1. Retinal-thalamic projections and other ocular measurements did not significantly differ between KO and WT mice. Conclusions: MaleChrdl1KO mice do not have the same anterior chamber abnormalities seen in humans withCHRDL1mutations. Therefore,Chrdl1KO mice do not recapitulate the human MGC1 phenotype. Nevertheless,Chrdl1plays a role during mouse ocular development because corneas in KO mice differ from those in WT mice.