A Mutation in LTBP2 Causes Congenital Glaucoma in Domestic Cats (Felis catus)
| Autor: | Todd E. Scheetz, S. Scott Whitmore, Stephen J. O'Brien, Markus H. Kuehn, Zhongyuan Zhao, Elizabeth M. Snella, Victor A. David, N. Matthew Ellinwood, Marilyn Menotti-Raymond, Gillian J. McLellan, Jackie K. Jens, Koren A. Lipsett |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Retinal Ganglion Cells 0301 basic medicine Candidate gene Intraocular pressure Pathology genetic structures Eye Diseases Genetic Linkage Glaucoma lcsh:Medicine Cat Diseases 0302 clinical medicine Medicine and Health Sciences Ectopia lentis lcsh:Science Lens (Anatomy) Genetics Mammals education.field_of_study Multidisciplinary CATS Mammalian Genomics Genomics Pedigree 3. Good health Phenotype Vertebrates Optic nerve Female Anatomy Sequence Analysis Research Article medicine.medical_specialty Animal Types Ocular Anatomy Population Biology Research and Analysis Methods Frameshift mutation Aqueous Humor 03 medical and health sciences Ocular System medicine Animals Domestic Animals education Molecular Biology Techniques Sequencing Techniques Molecular Biology Intraocular Pressure lcsh:R Organisms Correction Biology and Life Sciences Optic Nerve medicine.disease eye diseases Ophthalmology 030104 developmental biology Latent TGF-beta Binding Proteins Animal Genomics Mutation Amniotes 030221 ophthalmology & optometry Cats Eyes lcsh:Q sense organs Head Zoology Sequence Alignment |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 5, p e0154412 (2016) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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