July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Ocular manifestations of chordin-like 1 (Chrdl1) knockout mice
Author Affiliations & Notes
  • Yang Liu
    Schepens Eye Research Institute, MEE, HMS, Winchester, Massachusetts, United States
  • Matthew Warman
    Department of Genetics, Harvard Medical School, Orthopaedic Research Laboratories, Boston Children's Hospital, Boston, Massachusetts, United States
  • David A Sullivan
    Schepens Eye Research Institute, MEE, HMS, Winchester, Massachusetts, United States
  • Steven Hann
    Department of Genetics, Harvard Medical School, Orthopaedic Research Laboratories, Boston Children's Hospital, Boston, Massachusetts, United States
  • Di Chen
    Schepens Eye Research Institute, MEE, HMS, Winchester, Massachusetts, United States
    Department of Ophthalmology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing, China
  • Footnotes
    Commercial Relationships   Yang Liu, None; Matthew Warman, None; David Sullivan, None; Steven Hann, None; Di Chen, None
  • Footnotes
    Support  This research was supported by the Margaret S. Sinon Scholar in Ocular Surface Research fund, the One-Hundred-Talent Scholarship Program of Peking Union Medical College Hospital, and NIH National Eye Institute Core Grant P30EY003790
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4150. doi:
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    • Get Citation

      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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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