A defect in the NOG gene increases susceptibility to spontaneous superficial chronic corneal epithelial defects (SCCED) in boxer dogs

Kathryn M. Meurs, Keith Montgomery, Steven G. Friedenberg, Brian Williams, Brian C. Gilger

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Superficial chronic corneal epithelial defects (SCCEDs) are spontaneous corneal defects in dogs that share many clinical and pathologic characteristics to recurrent corneal erosions (RCE) in humans. Boxer dogs are predisposed to SCCEDs, therefore a search for a genetic defect was performed to explain this susceptibility. DNA was extracted from blood collected from Boxer dogs with and without SCCEDs followed by whole genome sequencing (WGS). RNA sequencing of corneal tissue and immunostaining of corneal sections from affected SCCED Boxer dogs with a deletion in the NOG gene and affected non-Boxer dogs without the deletion were performed.

RESULTS: A 30 base pair deletion at a splice site in Noggin (NOG) (Chr 9:31453999) was identified by WGS and was significantly associated (P < 0.0001) with Boxer SCCEDs compared to unaffected non-Boxer dogs. NOG, BMP4, MMP13, and NCAM1 all had significant fold reductions in expression and SHH was significantly increased in Boxers with the NOG deletion as identified by RNA-Seq. Corneal IHC from NOG deletion dogs with SCCEDs had lower NOG and significantly higher scores of BMP2.

CONCLUSIONS: Many Boxer dogs with SCCED have a genetic defect in NOG. NOG is a constitutive protein in the cornea which is a potent inhibitor of BMP, which likely regulate limbal epithelial progenitor cells (LEPC). Dysregulation of LEPC may play a role in the pathogenesis of RCE.

Original languageEnglish (US)
Article number254
JournalBMC Veterinary Research
Volume17
Issue number1
DOIs
StatePublished - Jul 26 2021

Bibliographical note

Funding Information:
The authors thank Damian Launer, Melissa Hamman, Erin Barr, and Beth Salmon for technical support. The authors also thank the University of North Carolina Histology Core for processing of the corneal histology and immunohistochemistry.

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • Boxer
  • Chronic
  • Corneal ulcer
  • NOG
  • Recurrent erosion
  • Superficial

PubMed: MeSH publication types

  • Journal Article

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