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Markus H. Kuehn, Gillian J. McLellan, Alexander Pfleging, Elizabeth M. Snella, N M. Ellinwood; Spontaneous Mutations In LTBP2 Are Associated With Congenital Glaucoma In Cats. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2424.
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We recently identified a novel, spontaneously occurring animal model of hereditary congenital glaucoma in a pedigree of Siamese cats. Affected cats have bilateral moderate buphthalmos, elevated intraocular pressure (IOP), and cupping of the optic nerve head. Clinical signs are obvious in affected kittens by 3 weeks of age. We previously mapped the genetic defect to a locus on feline chromosome B3. This study was conducted to determine which genetic defect causes the observed phenotype.
In order to facilitate the identification of the disease gene a breeding colony of affected cats was established. The sequences of several candidate genes were determined by direct DNA sequencing and candidate genetic loci were evaluated for linkage using nucleotide repeat markers. Histological examinations of the retina, optic nerve head, and anterior segment of affected and unaffected animals were conducted using tissue sections.
The mapped locus on chromosome B3 encompasses the gene LTBP2 which was screened as a candidate gene. Sequence analysis of this gene identified a 4-bp insertion disrupting the open reading frame and rapidly leads to premature truncation of the gene product in affected cats. Data from our breeding colony indicate that congenital glaucoma in cats is inherited in an autosomal recessive fashion, and that effect of the LTBP2 mutations is independent of the ‘Siamese’ genetic background. Histological examination of affected eyes suggested that the post-natal development of the structures of the ciliary cleft is arrested in these animals. The uveal trabecular meshwork and angular aqueous plexus remain rudimentary in affected animals and many outflow channels appear collapsed.
Our data demonstrate that a mutation in LTBP2 is the cause of congenital glaucoma in our colony cats. Data from several investigators have suggested that mutations in LTBP2 are also responsible for congenital glaucoma in Pakistani, Iranian, and Gypsy populations. Thus these animals represent a model for human disease and may aid in the development and translation of new treatment modalities, and/ or the elucidation of biochemical pathways involved in the morphogenesis of the anterior segment of the eye.
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