Journal article
A Mutation in LTBP2 Causes Congenital Glaucoma in Domestic Cats (Felis catus)
PloS one, Vol.11(5), pp.e0154412-e0154412
2016
DOI: 10.1371/journal.pone.0154412
PMCID: PMC4858209
PMID: 27149523
Abstract
The glaucomas are a group of diseases characterized by optic nerve damage that together represent a leading cause of blindness in the human population and in domestic animals. Here we report a mutation in LTBP2 that causes primary congenital glaucoma (PCG) in domestic cats. We identified a spontaneous form of PCG in cats and established a breeding colony segregating for PCG consistent with fully penetrant, autosomal recessive inheritance of the trait. Elevated intraocular pressure, globe enlargement and elongated ciliary processes were consistently observed in all affected cats by 8 weeks of age. Varying degrees of optic nerve damage resulted by 6 months of age. Although subtle lens zonular instability was a common feature in this cohort, pronounced ectopia lentis was identified in less than 10% of cats examined. Thus, glaucoma in this pedigree is attributed to histologically confirmed arrest in the early post-natal development of the aqueous humor outflow pathways in the anterior segment of the eyes of affected animals. Using a candidate gene approach, significant linkage was established on cat chromosome B3 (LOD 18.38, θ = 0.00) using tightly linked short tandem repeat (STR) loci to the candidate gene, LTBP2. A 4 base-pair insertion was identified in exon 8 of LTBP2 in affected individuals that generates a frame shift that completely alters the downstream open reading frame and eliminates functional domains. Thus, we describe the first spontaneous and highly penetrant non-rodent model of PCG identifying a valuable animal model for primary glaucoma that closely resembles the human disease, providing valuable insights into mechanisms underlying the disease and a valuable animal model for testing therapies.
Details
- Title: Subtitle
- A Mutation in LTBP2 Causes Congenital Glaucoma in Domestic Cats (Felis catus)
- Creators
- Markus H Kuehn - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaKoren A Lipsett - Department of Chemistry, Gettysburg College, Gettysburg, Pennsylvania, United States of AmericaMarilyn Menotti-Raymond - Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland, United States of AmericaS Scott Whitmore - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaTodd E Scheetz - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaVictor A David - Basic Research Laboratory, National Cancer Institute, Frederick, Maryland, United States of AmericaStephen J O'Brien - National Cancer InstituteZhongyuan Zhao - Department of Chemistry, Gettysburg College, Gettysburg, Pennsylvania, United States of AmericaJackie K Jens - Department of Animal Science, Iowa State University, Ames, Iowa, United States of AmericaElizabeth M Snella - Department of Animal Science, Iowa State University, Ames, Iowa, United States of AmericaN Matthew Ellinwood - Department of Veterinary Clinical Sciences, Iowa State University, Ames, Iowa, United States of AmericaGillian J McLellan - McPherson Eye Research Institute, Madison, Wisconsin, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.11(5), pp.e0154412-e0154412
- DOI
- 10.1371/journal.pone.0154412
- PMID
- 27149523
- PMCID
- PMC4858209
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- United States
- Grant note
- P30 EY016665 / NEI NIH HHS K08 EY018609 / NEI NIH HHS R01 EY022044 / NEI NIH HHS
- Language
- English
- Date published
- 2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Ophthalmology and Visual Sciences
- Record Identifier
- 9983979968502771
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