title: A Mini-review: Animal Models of GUCY2D Leber Congenital Amaurosis (LCA1).
abstract: GUCY2D encodes retinal guanylate cylase-1 (retGC1), a protein that plays a pivotal role in the recovery phase of phototransduction. Mutations in GUCY2D are associated with a leading cause of recessive Leber congenital amaurosis (LCA1). Patients present within the first year of life with aberrant or unrecordable electroretinogram (ERG), nystagmus and a relatively normal fundus. Aside from abnormalities in the outer segments of foveal cones and, in some patients, foveal cone loss, LCA1 patients retain normal retinal laminar architecture suggesting they may be good candidates for gene replacement therapy. Several animal models of LCA1, both naturally occurring and engineered, have been characterized and provide valuable tools for translational studies. This mini-review will summarize the phenotypes of these models and describe how each has been instrumental in proof of concept studies to develop a gene replacement therapy for GUCY2D-LCA1.
authors.affiliation: Departments of Ophthalmology and Molecular Genetics and Microbiology, University of Florida, 1600 SW Archer Rd, Academic Research Building Rm R2-236, 32621, Gainesville, FL, USA. Shannon.Boye@eye.ufl.edu.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Boye
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009154:Mutation; D011956:Receptors, Cell Surface / Q000235:genetics*; D012374:Rod Cell Outer Segment / Q000378:metabolism / Q000473:pathology
chemical_list: D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase
keywords: AAV; GC1; GUCY2D; Gene therapy; LCA1; Leber congenital amaurosis; RetGC1; Retinal guanylate cyclase