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Articles 61 - 90 of 90
Full-Text Articles in Medicine and Health Sciences
Radiation Hybrid Mapping Of Cataract Genes In The Dog, Linda S. Hunter, Duska J. Sidjanin, Jennifer L. Johnson, Barbara Zangerl, Francis Galibert, Catherine Andre, Ewen Kirkness, Elijah Talamas, Gregory M. Acland, Gustavo D. Aguirre
Radiation Hybrid Mapping Of Cataract Genes In The Dog, Linda S. Hunter, Duska J. Sidjanin, Jennifer L. Johnson, Barbara Zangerl, Francis Galibert, Catherine Andre, Ewen Kirkness, Elijah Talamas, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: To facilitate the molecular characterization of naturally occurring cataracts in dogs by providing the radiation hybrid location of 21 cataract-associated genes along with their closely associated polymorphic markers. These can be used for segregation testing of the candidate genes in canine cataract pedigrees. Methods: Twenty-one genes with known mutations causing hereditary cataracts in man and/or mouse were selected and mapped to canine chromosomes using a canine:hamster radiation hybrid RH5000 panel. Each cataract gene ortholog was mapped in relation to over 3,000 markers including microsatellites, ESTs, genes, and BAC clones. The resulting independently determined RH-map locations were compared with the …
Ocular Manifestations Of Selected Systemic Diseases, Gustavo D. Aguirre, Stephen L. Gross
Ocular Manifestations Of Selected Systemic Diseases, Gustavo D. Aguirre, Stephen L. Gross
Gustavo D. Aguirre, VMD, PhD
Systemic diseases can present ocular manifestations. In some cases, the ocular lesions are present along with other generalized lesions characteristic of the disease. In a few cases, however, only ocular lesions are present. The interpretation of these ophthalmologic findings, together with the generalized signs exhibited by the patient, are important in establishing a differential diagnosis and prognosis for the patient. This article reviews selected systemic diseases and their ocular manifestations. A more exhaustive review of the diseases has been already presented.
Intravitreal Injection Of Ciliary Neurotrophic Factor (Cntf) Causes Peripheral Remodeling And Does Not Prevent Photoreceptor Loss In Canine Rpgr Mutant Retina, William Beltran, Rong Wen, Gregory M. Acland, Gustavo D. Aguirre
Intravitreal Injection Of Ciliary Neurotrophic Factor (Cntf) Causes Peripheral Remodeling And Does Not Prevent Photoreceptor Loss In Canine Rpgr Mutant Retina, William Beltran, Rong Wen, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Ciliary neurotrophic factor (CNTF) rescues photoreceptors in several animal models of retinal degeneration and is currently being evaluated as a potential treatment for retinitis pigmentosa in humans. This study was conducted to test whether CNTF prevents photoreceptor cell loss in XLPRA2, an early onset canine model of X-linked retinitis pigmentosa caused by a frameshift mutation in RPGR exon ORF15. Four different treatment regimens of CNTF were tested in XLPRA2 dogs. Under anesthesia, the animals received at different ages an intravitreal injection of 12 μg of CNTF in the left eye. The right eye served as a control and was injected …
Linkage Disequilibrium Mapping In Domestic Dog Breeds Narrows The Progressive Rod-Cone Degeneration Interval And Identifies Ancestral Disease-Transmitting Chromosome, Orly Goldstein, Barbara Zangerl, Sue Pearce-Kelling, Duska J. Sidjanin, James W. Kijas, Jeanette Felix, Gregory M. Acland, Gustavo D. Aguirre
Linkage Disequilibrium Mapping In Domestic Dog Breeds Narrows The Progressive Rod-Cone Degeneration Interval And Identifies Ancestral Disease-Transmitting Chromosome, Orly Goldstein, Barbara Zangerl, Sue Pearce-Kelling, Duska J. Sidjanin, James W. Kijas, Jeanette Felix, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Canine progressive rod–cone degeneration (prcd) is a retinal disease previously mapped to a broad, gene-rich centromeric region of canine chromosome 9. As allelic disorders are present in multiple breeds, we used linkage disequilibrium (LD) to narrow the ∼6.4-Mb interval candidate region. Multiple dog breeds, each representing genetically isolated populations, were typed for SNPs and other polymorphisms identified from BACs. The candidate region was initially localized to a 1.5-Mb zero recombination interval between growth factor receptor-bound protein 2 (GRB2) and SEC14-like 1 (SEC14L). A fine-scale haplotype of the region was developed, which reduced the LD interval to 106 kb and identified …
Melanoma Of The Choroid In A Dog, Gustavo D. Aguirre, Gary Brown, Jerry A. Shields, Richard R. Dubielzig
Melanoma Of The Choroid In A Dog, Gustavo D. Aguirre, Gary Brown, Jerry A. Shields, Richard R. Dubielzig
Gustavo D. Aguirre, VMD, PhD
Intraocular tumors are rare in the dog. Of the reported neoplasms, melanomas are the most common. These tumors characteristically arise in the anterior uvea and secondarily infiltrate posteriorly into the choroid and/or anteriorly into the corneoscleral region. Advanced tumors may extend extraocularly. In the dog, isolated choroidal melanomas are extremely uncommon; to the authors' knowledge, only two cases have been previously reported. This report describes a pigmented choroidal tumor in a dog with clinical and histopathologic features resembling a benign melanoma.
Long-Term Restoration Of Rod And Cone Vision By Single Dose Raav-Mediated Gene Transfer To The Retina In A Canine Model Of Childhood Blindness, Gregory M. Acland, Gustavo D. Aguirre, Jean Bennett, Tomas S. Aleman, Artur V. Cideciyan, Jeannette Bennicelli, Nadine S. Dejneka, Susan E. Pearce-Kelling, Albert M. Maguire, Krzysztof Palczewski, William W. Hauswirth, Samuel G. Jacobson
Long-Term Restoration Of Rod And Cone Vision By Single Dose Raav-Mediated Gene Transfer To The Retina In A Canine Model Of Childhood Blindness, Gregory M. Acland, Gustavo D. Aguirre, Jean Bennett, Tomas S. Aleman, Artur V. Cideciyan, Jeannette Bennicelli, Nadine S. Dejneka, Susan E. Pearce-Kelling, Albert M. Maguire, Krzysztof Palczewski, William W. Hauswirth, Samuel G. Jacobson
Gustavo D. Aguirre, VMD, PhD
The short- and long-term effects of gene therapy using AAV-mediated RPE65 transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by RPE65 deficiency. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine RPE65 cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no …
Operating In The Dark: A Night-Vision System For Surgery In Retinas Susceptible To Light Damage, András M. Komáromy, Gregory M. Acland, Gustavo D. Aguirre
Operating In The Dark: A Night-Vision System For Surgery In Retinas Susceptible To Light Damage, András M. Komáromy, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
A standard operating microscope was modified with a bandpass infrared filter in the light path and infrared image intensifiers for each of the 2 eyepieces. We evaluated this system for subretinal injections in normal control dogs and those with a mutation in the rhodopsin gene. Rhodopsin-mutant dogs are a model for human autosomal dominant retinitis pigmentosa, and their retinas degenerate faster when exposed to modest light levels as used in routine clinical examinations. We showed that the mutant retinas developed severe generalized degeneration when exposed to the standard operating microscope light but not the infrared light. The modified operating microscope …
Electroretinography - Are We Misusing An Excellent Diagnostic Tool?, Gustavo D. Aguirre
Electroretinography - Are We Misusing An Excellent Diagnostic Tool?, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
No abstract provided.
Exclusion Of The Unfolded Protein Response In Light-Induced Retinal Degeneration In The Canine T4r Rho Model Of Autosomal Dominant Retinitis Pigmentosa, Stefania Marsilli, Sem Genini, Raghavi Sudharsan, Jeremy Gingrich, Gustavo D. Aguirre, William Beltran
Exclusion Of The Unfolded Protein Response In Light-Induced Retinal Degeneration In The Canine T4r Rho Model Of Autosomal Dominant Retinitis Pigmentosa, Stefania Marsilli, Sem Genini, Raghavi Sudharsan, Jeremy Gingrich, Gustavo D. Aguirre, William Beltran
Gustavo D. Aguirre, VMD, PhD
Purpose To examine the occurrence of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) following acute light damage in the naturally-occurring canine model of RHO-adRP (T4R RHOdog). Methods The left eyes of T4R RHOdogs were briefly light-exposed and retinas collected 3, 6 and 24 hours later. The contra-lateral eyes were shielded and used as controls. To evaluate the time course of cell death, histology and TUNEL assays were performed. Electron microscopy was used to examine ultrastructural alterations in photoreceptors at 15 min, 1 hour, and 6 hours after light exposure. Gene expression of markers of ER stress and …
Genetic And Phenotypic Variations Of Inherited Retinal Diseases In Dogs: The Power Of Within- And Across-Breed Studies, Keiko Miyadera, Gregory M. Acland, Gustavo D. Aguirre
Genetic And Phenotypic Variations Of Inherited Retinal Diseases In Dogs: The Power Of Within- And Across-Breed Studies, Keiko Miyadera, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than …
Electroretinography In Veterinary Ophthalmology, Gustavo D. Aguirre
Electroretinography In Veterinary Ophthalmology, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
No abstract provided.
Immunolocalization Of Ciliary Neurotrophic Factor Receptor Α (Cntfrα) In Mammalian Photoreceptor Cells, William Beltran, Hermann Rohrer, Gustavo D. Aguirre
Immunolocalization Of Ciliary Neurotrophic Factor Receptor Α (Cntfrα) In Mammalian Photoreceptor Cells, William Beltran, Hermann Rohrer, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
PURPOSE: To characterize the site of expression of the α subunit of the receptor for ciliary neurotrophic factor (CNTFRα) in the retina of a variety of mammalian species, and determine whether CNTFRα is localized to photoreceptor cells. METHODS: The cellular distribution of CNTFRα (protein) was examined by immunocytochemistry in the adult retinas of several mammalian species that included mouse, rat, dog, cat, sheep, pig, horse, monkey, and human. Developing retinas from 3-day-old and 6-day-old rats were also included in this study. The molecular weight of CNTFRα in rat, dog, cat, pig, and human retinas was determined by immunoblotting. RESULTS: CNTFRα …
Exploring Human/Animal Intersections: Converging Lines Of Evidence In Comparative Models Of Aging, John Q. Trojanowski, Joan C. Hendricks, Kathryn Jedrziewski, F. Brad Johnson, Kathryn E. Michel, Rebecka S. Hess, Michael P. Cancro, Margaret M. Sleeper, Robert Pignolo, Karen L. Teff, Gustavo D. Aguirre, Virginia Man-Yee Lee, Dennis F. Lawler, Allan I. Pack, Peter F. Davies
Exploring Human/Animal Intersections: Converging Lines Of Evidence In Comparative Models Of Aging, John Q. Trojanowski, Joan C. Hendricks, Kathryn Jedrziewski, F. Brad Johnson, Kathryn E. Michel, Rebecka S. Hess, Michael P. Cancro, Margaret M. Sleeper, Robert Pignolo, Karen L. Teff, Gustavo D. Aguirre, Virginia Man-Yee Lee, Dennis F. Lawler, Allan I. Pack, Peter F. Davies
Gustavo D. Aguirre, VMD, PhD
At a symposium convened on March 8, 2007 by the Institute on Aging at the University of Pennsylvania, researchers from the University’s Schools of Medicine and Veterinary Medicine explored the convergence of aging research emerging from the two schools. Studies in human patients, animal models, and companion animals have revealed different but complementary aspects of the aging process, ranging from fundamental biologic aspects of aging to the treatment of age-related diseases, both experimentally and in clinical practice. Participants concluded that neither animal nor human research alone will provide answers to most questions about the aging process. Instead, an optimal translational …
Congenital Stationary Night Blindness In The Dog: Common Mutation In The Rpe65 Gene Indicates Founder Effect, Gustavo D. Aguirre, Victoria Baldwin, Sue Pearce-Kelling, Kristina Narfström, Kunal Ray, Gregory M. Acland
Congenital Stationary Night Blindness In The Dog: Common Mutation In The Rpe65 Gene Indicates Founder Effect, Gustavo D. Aguirre, Victoria Baldwin, Sue Pearce-Kelling, Kristina Narfström, Kunal Ray, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
Purpose: To clone and characterize the canine RPE65 cDNA from normal dog, examine for mutations, and establish if the mutation identified in Swedish briard dogs with retinal dystrophy is present in dogs of the same breed that originated from the United States and other countries, and are affected with congenital stationary night blindness. Methods: Fifteen briard dogs were studied, of which 10 were affected with csnb, and five were clinically normal. In addition, we tested samples from four Swedish dogs, and samples from a briard affected with progressive retinal atrophy. RPE65 cDNA was cloned a from retinal cDNA library by …
Canine And Human Visual Cortex Intact And Responsive Despite Early Retinal Blindness From Rpe65 Mutation, Geoffrey K. Aguirre, András M. Komáromy, Artur V. Cideciyan, David H. Brainard, Tomas S. Aleman, Alejandro J. Roman, Brian B. Avants, James C. Gee, Marc Korczykowski, William W. Hauswirth, Gregory M. Acland, Gustavo D. Aguirre, Samuel G. Jacobson
Canine And Human Visual Cortex Intact And Responsive Despite Early Retinal Blindness From Rpe65 Mutation, Geoffrey K. Aguirre, András M. Komáromy, Artur V. Cideciyan, David H. Brainard, Tomas S. Aleman, Alejandro J. Roman, Brian B. Avants, James C. Gee, Marc Korczykowski, William W. Hauswirth, Gregory M. Acland, Gustavo D. Aguirre, Samuel G. Jacobson
Gustavo D. Aguirre, VMD, PhD
Background RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA). Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans …
Diseases Of The Retinal Pigment Epithelium-Photoreceptor Complex In Nonrodent Animal Models, Gustavo D. Aguirre, Jharna Ray, Lawrence E. Stramm
Diseases Of The Retinal Pigment Epithelium-Photoreceptor Complex In Nonrodent Animal Models, Gustavo D. Aguirre, Jharna Ray, Lawrence E. Stramm
Gustavo D. Aguirre, VMD, PhD
Book Overview: The retinal pigment epithelium is a critical tissue within the eye. It lies directly behind the retina, where it provides metabolic support to the photoreceptors and controls their local environment. As a result, the RPE is vital to retinal function, but also a site of aging and disease that cause dysfunction and visual loss. This book brings together comprehensive reviews of basic and clinical science concerning the RPE. It is organized to juxtapose chapters on RPE disease with chapters on the underlying pathophysiology. These include up-to-date accounts of growth factors, laser effects, proliferative vitreoretinopathy, Bruch's membrane pathology, as …
Cloning Of The Canine Abca4 Gene And Evaluation In Canine Cone-Rod Dystrophies And Progressive Retinal Atrophies, James K. Kijas, Barbara Zangerl, Brian Miller, Jacque Nelson, Ewen F. Kirkness, Gustavo D. Aguirre, Gregory M. Acland
Cloning Of The Canine Abca4 Gene And Evaluation In Canine Cone-Rod Dystrophies And Progressive Retinal Atrophies, James K. Kijas, Barbara Zangerl, Brian Miller, Jacque Nelson, Ewen F. Kirkness, Gustavo D. Aguirre, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
PURPOSE: To characterize a novel early onset canine retinal disease, and evaluate the ATP-binding cassette transporter gene ABCA4 as a potential candidate gene in this and other canine retinal degenerations. METHODS: Retinal disease was characterized ophthalmoscopically and electroretinographically in two pit bull terrier dogs and their purpose-bred descendants. All 50 exons of the canine ABCA4 gene were amplified, cloned and sequenced from retinal mRNA of a normal, a carrier and an affected animal, and polymorphisms identified. The latter were used to search for association between ABCA4 and retinal disease both within the study pedigrees and in additional canine breeds segregating …
Cloning And Characterization Of Canine Pax6 And Evaluation As A Candidate Gene In A Canine Model Of Aniridia, Linda S. Hunter, Duska J. Sidjanin, Manuel Villagrasa Hijar, Jennifer L. Johnson, Ewen Kirkness, Gregory M. Acland, Gustavo D. Aguirre
Cloning And Characterization Of Canine Pax6 And Evaluation As A Candidate Gene In A Canine Model Of Aniridia, Linda S. Hunter, Duska J. Sidjanin, Manuel Villagrasa Hijar, Jennifer L. Johnson, Ewen Kirkness, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: Mutations in PAX6 cause human aniridia. The small eye (sey) mouse represents an animal model for aniridia. However, no large animal model currently exists. We cloned and characterized canine PAX6, and evaluated PAX6 for causal associations with inherited aniridia in dogs. Methods: Canine PAX6 was cloned from a canine retinal cDNA library using primers designed from human and mouse PAX6 consensus sequences. An RH3000 radiation hybrid panel was used to localize PAX6 within the canine genome. Genomic DNA was extracted from whole blood of dogs with inherited aniridia, and association testing was performed using markers on CFA18. Fourteen PAX6 …
Cloning Of Canine Galactokinase (Galk1) And Evaluation As A Candidate Gene For Hereditary Cataracts In Labrador Retrievers, Duska J. Sidjanin, John L. Mcelwee, Brian Miller, Gustavo D. Aguirre
Cloning Of Canine Galactokinase (Galk1) And Evaluation As A Candidate Gene For Hereditary Cataracts In Labrador Retrievers, Duska J. Sidjanin, John L. Mcelwee, Brian Miller, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
We identified a pedigree of Labrador retrievers (LR) that develop hereditary cataracts between 6 and 18 months of age. In humans, galactokinase deficiency is an autosomal recessive disorder characterized by juvenile onset of cataracts.1 In order to evaluate GALK1 as a candidate gene, we cloned and sequenced the canine GALK1 gene and tested a single nucleotide polymorphism (SNP) in the gene for segregation with cataracts in the LR pedigree.
A Meiotic Linkage Map Of The Silver Fox, Aligned And Compared To The Canine Genome, Anna V. Kukekova, Lyudmila N. Trut, Irina N. Oskina, Jennifer L. Johnson, Svetlana V. Temnykh, Anastasiya V. Kharlamova, Darya V. Shepeleva, Rimma G. Gulievich, Svetlana G. Shikhevich, Alexander S. Graphodatsky, Gustavo D. Aguirre, Gregory M. Acland
A Meiotic Linkage Map Of The Silver Fox, Aligned And Compared To The Canine Genome, Anna V. Kukekova, Lyudmila N. Trut, Irina N. Oskina, Jennifer L. Johnson, Svetlana V. Temnykh, Anastasiya V. Kharlamova, Darya V. Shepeleva, Rimma G. Gulievich, Svetlana G. Shikhevich, Alexander S. Graphodatsky, Gustavo D. Aguirre, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
A meiotic linkage map is essential for mapping traits of interest and is often the first step toward understanding a cryptic genome. Specific strains of silver fox (a variant of the red fox, Vulpes vulpes), which segregate behavioral and morphological phenotypes, create a need for such a map. One such strain, selected for docility, exhibits friendly dog-like responses to humans, in contrast to another strain selected for aggression. Development of a fox map is facilitated by the known cytogenetic homologies between the dog and fox, and by the availability of high resolution canine genome maps and sequence data. Furthermore, the …
Age-Dependent Disease Expression Determines Remodeling Of The Retinal Mosaic In Carriers Of Rpgr Exon Orfn15 Mutations, William Beltran, Gregory M. Acland, Gustavo D. Aguirre
Age-Dependent Disease Expression Determines Remodeling Of The Retinal Mosaic In Carriers Of Rpgr Exon Orfn15 Mutations, William Beltran, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
PURPOSE. To characterize the retinal histopathology in carriers of X-linked progressive retinal atrophy (XLPRA1 and XLPRA2), two canine models of X-linked retinitis pigmentosa caused, respectively, by a stop and a frameshift mutation in RPGRORF15. METHODS. Retinas of XLPRA2 and XLPRA1 carriers of different ages were processed for morphologic evaluation, TUNEL assay, and immunohistochemistry. Cell-specific markers were used to examine retinal remodeling events. RESULTS. A mosaic pattern composed of patches of diseased and normal retina was first detected in XLPRA2 carriers at 4.9 weeks of age. A peak of photoreceptor cell death led to focal rod loss; however, in these patches …
Calcium Channel Blocker D-Cis-Diltiazem Does Not Slow Retinal Degeneration In The Pde6b Mutant Rcd1 Canine Model Of Retinitis Pigmentosa, Susan E. Pearce-Kelling, Tomas S. Aleman, Amanda Nickle, Alan M. Laties, Gustavo D. Aguirre, Samuel G. Jacobson, Gregory M. Acland
Calcium Channel Blocker D-Cis-Diltiazem Does Not Slow Retinal Degeneration In The Pde6b Mutant Rcd1 Canine Model Of Retinitis Pigmentosa, Susan E. Pearce-Kelling, Tomas S. Aleman, Amanda Nickle, Alan M. Laties, Gustavo D. Aguirre, Samuel G. Jacobson, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
Purpose: D-cis-diltiazem, a calcium channel blocker, has been reported to enhance photoreceptor survival in the rd mouse, a model of retinitis pigmentosa (RP) resulting from mutation of the PDE6B gene. We tested the hypothesis that diltiazem treatment would similarly rescue the canine rcd1 model of RP, which is also caused by a null mutation in the PDE6B gene. Methods: D-cis-diltiazem was delivered orally twice daily to rcd1 affected dogs beginning at 4 weeks of age; untreated age-matched rcd1 dogs served as controls. At 14 weeks, electroretinograms (ERG) were performed on all animals; 14 dogs were euthanized at this age, and …
Blinded By The Light: Retinal Phototoxicity In The Context Of Safety Studies, Maria Cristina De Vera Mudry, Sven Kronenberg, Shun-Ichiro Komatsu, Gustavo D. Aguirre
Blinded By The Light: Retinal Phototoxicity In The Context Of Safety Studies, Maria Cristina De Vera Mudry, Sven Kronenberg, Shun-Ichiro Komatsu, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
No abstract provided.
Breed Relationships Facilitate Fine-Mapping Studies: A 7.8-Kb Deletion Cosegregates With Collie Eye Anomaly Across Multiple Dog Breeds, Heidi G. Parker, Anna V. Kukekova, Danya T. Akey, Orly Goldstein, Ewen F. Kirkness, Kathleen C. Baysac, Dana S. Mosher, Gustavo D. Aguirre, Gregory M. Acland, Elaine A. Ostrander
Breed Relationships Facilitate Fine-Mapping Studies: A 7.8-Kb Deletion Cosegregates With Collie Eye Anomaly Across Multiple Dog Breeds, Heidi G. Parker, Anna V. Kukekova, Danya T. Akey, Orly Goldstein, Ewen F. Kirkness, Kathleen C. Baysac, Dana S. Mosher, Gustavo D. Aguirre, Gregory M. Acland, Elaine A. Ostrander
Gustavo D. Aguirre, VMD, PhD
The features of modern dog breeds that increase the ease of mapping common diseases, such as reduced heterogeneity and extensive linkage disequilibrium, may also increase the difficulty associated with fine mapping and identifying causative mutations. One way to address this problem is by combining data from multiple breeds segregating the same trait after initial linkage has been determined. The multibreed approach increases the number of potentially informative recombination events and reduces the size of the critical haplotype by taking advantage of shortened linkage disequilibrium distances found across breeds. In order to identify breeds that likely share a trait inherited from …
Canine Multifocal Retinopathy In The Australian Shepherd: A Case Report, Ingo Hoffmann, Karina E. Guziewicz, Barbara Zangerl, Gustavo D. Aguirre, Christian Y. Mardin
Canine Multifocal Retinopathy In The Australian Shepherd: A Case Report, Ingo Hoffmann, Karina E. Guziewicz, Barbara Zangerl, Gustavo D. Aguirre, Christian Y. Mardin
Gustavo D. Aguirre, VMD, PhD
A 1-year-old Australian Shepherd (AS) was presented for a routine hereditary eye examination. During the examination multiple raised, brown to orange lesions were noted in the fundus, which could not be attributed to a known retinal disease in this breed. As they clinically most closely resembled canine multifocal retinopathy (cmr) and no indication of an acquired condition was found, genetic tests for BEST1 gene mutations were performed. These showed the dog to be homozygous for the cmr1 (C73T/R25X) gene defect. Furthermore, ultrasound (US), electroretinography (ERG), and optical coherence tomography were performed, confirming changes typical for cmr. Subsequently, the AS pedigree …
Animal Model Of Human Disease: Mucopolysaccharidosis Type Vii (Sly Syndrome). Beta-Glucuronidase-Deficient Mucopolysaccharidosis In The Dog, Mark E. Haskins, Gustavo D. Aguirre, Peter F. Jezyk, Edward H. Schuchman, Robert J. Desnick, Donald F. Patterson
Animal Model Of Human Disease: Mucopolysaccharidosis Type Vii (Sly Syndrome). Beta-Glucuronidase-Deficient Mucopolysaccharidosis In The Dog, Mark E. Haskins, Gustavo D. Aguirre, Peter F. Jezyk, Edward H. Schuchman, Robert J. Desnick, Donald F. Patterson
Gustavo D. Aguirre, VMD, PhD
No abstract provided.
A Naturally Occurring Mutation Of The Opsin Gene (T4r) In Dogs Affects Glycosylation And Stability Of The G Protein-Coupled Receptor, Li Zhu, Geeng-Fu Jang, Beata Jastrzebska, Slawomir Filipek, Susan E. Pearce-Kelling, Gustavo D. Aguirre, Ronald E. Stenkamp, Gregory M. Acland, Krzysztof Palczewski
A Naturally Occurring Mutation Of The Opsin Gene (T4r) In Dogs Affects Glycosylation And Stability Of The G Protein-Coupled Receptor, Li Zhu, Geeng-Fu Jang, Beata Jastrzebska, Slawomir Filipek, Susan E. Pearce-Kelling, Gustavo D. Aguirre, Ronald E. Stenkamp, Gregory M. Acland, Krzysztof Palczewski
Gustavo D. Aguirre, VMD, PhD
Rho (rhodopsin; opsin plus 11-cis-retinal) is a prototypical G protein-coupled receptor responsible for the capture of a photon in retinal photoreceptor cells. A large number of mutations in the opsin gene associated with autosomal dominant retinitis pigmentosa have been identified. The naturally occurring T4R opsin mutation in the English mastiff dog leads to a progressive retinal degeneration that closely resembles human retinitis pigmentosa caused by the T4K mutation in the opsin gene. Using genetic approaches and biochemical assays, we explored the properties of the T4R mutant protein. Employing immunoaffinity-purified Rho from affected RHOT4R/T4R dog retina, we found …
Analysis Of Six Candidate Genes As Potential Modifiers Of Disease Expression In Canine Xlpra1, A Model For Human X-Linked Retinitis Pigmentosa 3, Richard Guyon, Susan E. Pearce-Kelling, Caroline J. Zeiss, Gregory M. Acland, Gustavo D. Aguirre
Analysis Of Six Candidate Genes As Potential Modifiers Of Disease Expression In Canine Xlpra1, A Model For Human X-Linked Retinitis Pigmentosa 3, Richard Guyon, Susan E. Pearce-Kelling, Caroline J. Zeiss, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: Canine X-linked progressive retinal atrophy (XLPRA) is caused by mutations in RPGR exon ORF15, which is also a mutation hotspot in human X-linked retinitis pigmentosa 3 (RP3). The XLPRA1 form of disease has shown extensive phenotypic variability in a colony of dogs that all inherited the same mutant X-chromosome. This variability in onset and severity makes XLPRA1 a valuable model to use to identify genes influencing photoreceptors degeneration in dog and to elucidate molecular mechanisms underlying RP in its human homolog. In this study, RPGRIP1, RANBP2, NPM1, PDE6D, NPHP5, and ABCA4 genes were selected on the basis of interaction …
Blindness Due To Polymicrogyria And Asymmetrical Dilation Of The Lateral Ventricles In Standard Poodles, Thomas J. Van Winkle, John C. Fyfe, Betsy Dayrell-Hart, Gustavo D. Aguirre, Gregory M. Acland, Donald F. Patterson
Blindness Due To Polymicrogyria And Asymmetrical Dilation Of The Lateral Ventricles In Standard Poodles, Thomas J. Van Winkle, John C. Fyfe, Betsy Dayrell-Hart, Gustavo D. Aguirre, Gregory M. Acland, Donald F. Patterson
Gustavo D. Aguirre, VMD, PhD
Polymicrogyria and asymmetric dilation of the lateral ventricles were seen in related Standard poodles that had cortical blindness. Three of the affected dogs also had gait and postural abnormalities, and one of these had seizures.Two of the affected dogs were littermates. Thorough ophthalmologic and neurologic examinations (including electroretinography, electromyography, cerebrospinal fluid analysis, plain radiographs, and computerized tomography scans) revealed no significant abnormalities outside of the brain that would account for the blindness. Computerized tomography scans in three dogs demonstrated bilateral dilation of the lateral ventricles which was more severe in the right. All dogs were necropsied between 5 and 9 …
Rpgrip1 And Cone-Rod Dystrophy In Dogs, Tatyana N. Kuznetsova, Barbara Zangerl, Gustavo D. Aguirre
Rpgrip1 And Cone-Rod Dystrophy In Dogs, Tatyana N. Kuznetsova, Barbara Zangerl, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Cone–rod dystrophies (crd) represent a group of progressive inherited blinding diseases characterized by primary dysfunction and loss of cone photoreceptors accompanying or preceding rod death. Recessive crd type 1 was described in dogs associated with an RPGRIP1 exon 2 mutation, but with lack of complete concordance between genotype and phenotype. This review highlights role of the RPGRIP1, a component of complex protein networks, and its function in the primary cilium, and discusses the potential mechanisms of genotype–phenotype discordance observed in dogs with the RPGRIP1 mutation.