The mutant dog promises to be always a valuable model for preclinical trials of such therapy. Materials and Methods Ethics Statement All procedures were in compliance with the ARVO statement for the Use of Animals in Ophthalmic and Vision Research and approved by the Michigan State University Institutional Animal Care and Use Committee (AUF number 05-11-106-00; Institutional NIH/PHS Animal Welfare Assurance number A3955-01). Electroretinography To assess rod and cone photoreceptor function, electroretinograms (ERGs) were recorded using a modification of a XL388 previously described technique [26]. stop codon. Immunohistochemistry (IHC) of pre-degenerate retinal sections from a young affected dog showed absence of labeling using a C-terminal CNGB1 antibody. Whereas an antibody directed against the N-terminus of the protein, which also recognizes the glutamic acid rich proteins arising from alternative splicing of the CNGB1 transcript (upstream of the premature stop codon), labeled rod outer segments. CNGB1 combines with CNGA1 to form the rod cyclic nucleotide gated channel and previous studies have shown the requirement of CNGB1 for normal targeting of CNGA1 to the rod outer segment. In keeping with these previous observations, IHC showed a lack of detectable CNGA1 protein in the rod outer segments of the affected dog. A population study did not identify the mutation in PRA-affected dogs in other breeds and documented that the mutation accounts for 70% of cases of Papillon PRA in our PRA-affected canine DNA bank. mutations are one cause of autosomal recessive RP making the mutant dog a valuable large animal model of the condition. Introduction Retinitis pigmentosa (RP) is the leading cause of inherited blindness in humans affecting about 1 in 4,000 people [1]. It can be inherited in a dominant, recessive or X-linked fashion and shows considerable locus heterogeneity, with mutations in over 40 genes identified as causing non-syndromic RP (RetNet: https://sph.uth.edu/retnet/sum-dis.htm). Proteins encoded by these genes are necessary for a variety of functions within photoreceptors and their supporting cells. The age at onset and rate of progression of RP vary such that some patients have a history of night blindness from childhood while others may not notice symptoms until they are adults. The variability depends on the gene involved and the effect of the mutation on gene function, but there is also variability between patients with XL388 the same mutation [2], [3]. Rod photoreceptors are affected initially, resulting in loss of night (rod-mediated) vision and constriction of the visual fields. Loss of cone-mediated (daytime and color) vision may occur secondarily to rod-loss, even when RP is caused by a mutation of a gene exclusively expressed in rods, and can lead to complete blindness. Retinal dystrophies analogous to RP occur in dogs, with reports of such conditions in over 100 different breeds [4]. The canine RP equivalent is known as progressive retinal atrophy (PRA) [5], [6]. The gene mutations underlying several forms of PRA have been identified and many have proven to be in genes analogous to those known to cause RP [7], [8], [9], [10], [11], [12], [13] or in some instances have suggested new candidate genes for investigation in RP patients [14], [15], [16]. Spontaneously occurring retinal dystrophies in canine models are of particular interest because the canine eye is similar in size to the human eye. This morphological similarity allows for identical surgical approaches for intravitreal Opn5 and subretinal injection of therapeutic agents and testing for approaches such as implantation of intravitreal sustained-release devices. An additional advantage of canine models over rodent models is that the canine eye has regions of higher photoreceptor density (of both rods and cones), namely the area XL388 centralis and the visual streak that are somewhat analogous to the human macula [17]. In contrast, the retina of laboratory rodents lacks an equivalent region having an even density of photoreceptors across the retina [18]. Dogs with.