Radiation Hybrid Map, Physical Map, And Low-Pass Genomic Sequence Of The Canine Prcd Region On Cfa9 And Comparative Mapping With The Syntenic Region On Human Chromosome 17 ☆, Duska Sidjanin, B Miller, J. W. Kijas, J Mcelwee, Jarek Pillardy, J Malek, G Pai, Tamara Feldblyum, C Fraser, Gregory Acland, Gustavo Aguirre
Jan 2003
Radiation Hybrid Map, Physical Map, And Low-Pass Genomic Sequence Of The Canine Prcd Region On Cfa9 And Comparative Mapping With The Syntenic Region On Human Chromosome 17 ☆, Duska Sidjanin, B Miller, J. W. Kijas, J Mcelwee, Jarek Pillardy, J Malek, G Pai, Tamara Feldblyum, C Fraser, Gregory Acland, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
Progressive rod–cone degeneration (prcd) is a canine retinal disease that maps to the centromeric end of CFA9 in a region of synteny with the distal part of HSA17q. As such,prcd has been postulated as the only animal model of RP17, a human retinitis pigmentosa locus that maps to 17q22. In an effort to establish more detailed regions of synteny between dog CFA9 and the HSA17q–ter region, we created a robust gene-enriched CFA9-RH083000 map with 34 gene-based markers and 12 microsatellites, with the highest resolution and number of markers for the centromeric end of CFA9. Furthermore, we …
Comparative Analysis, Gene Organization And Expression Of Canine Tcte1l, Kui Li, Qi Zhang, Jennifer L. Johnson, Gustavo D. Aguirre
Dec 2002
Comparative Analysis, Gene Organization And Expression Of Canine Tcte1l, Kui Li, Qi Zhang, Jennifer L. Johnson, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
The murine t-complex-associated testis-expressed 1-like gene (TCTE1L) of the dog was cloned, characterized, and compared to the human ortholog. The characterized region of cDNA includes 351 bp of coding sequence which encodes a protein of 116 amino acids. The canine gene, spanning about 8.5 kb sequence, consists of 5 exons, with the initiation and stop codons found in the first and last exons, respectively. The comparative analyses reveal the evolutionarily conserved exonic and intronic regions, as well as gene flanking sequences. A 2.1 kb transcript was ubiquitously expressed in all the tissues examined, and secondarily down-expressed in the …
Molecular Cloning, Characterization And Expression Of A Novel Retinal Clusterin-Like Protein Cdna, Qi Zhang, Kunal Ray, Gregory M. Acland, Jill M. Czarnecki, Gustavo D. Aguirre
Jan 2000
Molecular Cloning, Characterization And Expression Of A Novel Retinal Clusterin-Like Protein Cdna, Qi Zhang, Kunal Ray, Gregory M. Acland, Jill M. Czarnecki, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
A novel gene expressed predominantly in retina, but detected at a conspicuously lower level in retina of canine progressive rod cone degeneration (prcd), has been identified by suppression subtractive hybridization and retinal cDNA library screening. The characterized region of cDNA of the novel gene includes 1017 nucleotides of coding sequence predicted to encode a protein of 338 amino acids (Mr 39 389), 791 nucleotides of 5′-untranslated region (UTR), and 300 nucleotides of 3′-UTR including the poly(A)+ tail. Multiple transcripts were detected in retina by Northern blot analysis, and a lower level of expression was observed in …
Evaluation Of Cgmp-Phosphodiesterase (Pde) Subunits For Causal Association With Rod–Cone Dysplasia 2 (Rcd2), A Canine Model Of Abnormal Retinal Cgmp Metabolism, Weiquan Wang, Gregory Acland, Kunal Ray, Gustavo Aguirre
Sep 1999
Evaluation Of Cgmp-Phosphodiesterase (Pde) Subunits For Causal Association With Rod–Cone Dysplasia 2 (Rcd2), A Canine Model Of Abnormal Retinal Cgmp Metabolism, Weiquan Wang, Gregory Acland, Kunal Ray, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
Rod-cone dysplasia types 1 (rcd1; Irish setter) and 2 (rcd2; collie) in dogs are early onset forms of progressive retinal atrophy (PRA) which serve as models of retinitis pigmentosa(RP) in humans. As bothrcd1 and rcd2 result from abnormal retinal cGMP metabolism associated with a deficiency in cGMP-phosphodiesterase (PDE) activity, and a nonsense mutation in the PDE6B subunit gene has been shown to cause rcd1, the genes encoding the four subunits of the PDE complex (PDE6A, PDE6B, PDE6G and PDE6D) make compelling candidates for the rcd2 locus. We adopted diverse strategies to evaluate causal association of the four PDE subunit genes …
Timp-1 Expression Is Increased In X-Linked Progressive Retinal Atrophy Despite Its Exclusion As A Candidate Gene, Caroline Zeiss, Gregory M. Acland, Gustavo D. Aguirre, Kunal Ray
Dec 1998
Timp-1 Expression Is Increased In X-Linked Progressive Retinal Atrophy Despite Its Exclusion As A Candidate Gene, Caroline Zeiss, Gregory M. Acland, Gustavo D. Aguirre, Kunal Ray
Gustavo D. Aguirre, VMD, PhD
X-linked progressive retinal atrophy (XLPRA) is the only known natural animal model for X-linked retinitis pigmentosa (XLRP), a blinding disorder in man. The tissue inhibitor metalloproteinase 1 gene (TIMP-1), present in close proximity to one of the two XLRPloci, was tested as a candidate for XLPRA, by first characterizing the cDNA and gene from a normal dog. The cloned canine TIMP-1 cDNA is predicted to encode a protein of 207 amino acids with 66–83% identity in the deduced aa sequence with homologous mammalian genes. No sequence difference in the coding sequence of …
Canine Rod Photoreceptor Cgmp-Gated Channel Protein Α-Subunit: Studies On The Expression Of The Gene And Characterization Of The Cdna, Qi Zhang, Sue Pearce-Kelling, Gregory Acland, Gustavo Aguirre, Kunal Ray
Jul 1997
Canine Rod Photoreceptor Cgmp-Gated Channel Protein Α-Subunit: Studies On The Expression Of The Gene And Characterization Of The Cdna, Qi Zhang, Sue Pearce-Kelling, Gregory Acland, Gustavo Aguirre, Kunal Ray
Gustavo D. Aguirre, VMD, PhD
Rod photoreceptor cyclic GMP gated-channel protein is a key component of the visual transduction cascade in the vertebrate retina. The protein is composed of at least two subunits (α and β). Mutations in the α-subunit (CNGC1) have been shown to cause retinitis pigmentosa (RP) in humans. Several heterogeneous canine retinal diseases, which are clinically similar to RP, are known collectively as progressive retinal atrophy (PRA) and occur in dogs in a breed-specific manner. For the purpose of examining CNGC1 gene as a candidate for PRA, we report here the characterization of canine CNGC1 cDNA, and examine the expression of the …
Differential Expression Of Photoreceptor-Specific Proteins During Disease And Degeneration In The Progressive Rod-Cone Degeneration (Prcd) Retina, Kathryn Gropp, Jun Huang, Gustavo Aguirre
May 1997
Differential Expression Of Photoreceptor-Specific Proteins During Disease And Degeneration In The Progressive Rod-Cone Degeneration (Prcd) Retina, Kathryn Gropp, Jun Huang, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
Progressive rod-cone degeneration (prcd) is a late-onset hereditary retinal degeneration characterized by normal development of photoreceptors prior to degeneration and death of visual cells. We reported previously that expression of opsin mRNA and protein decreases prior to visual cell degeneration. To examine the specificity of this reduction, we have used immunocytochemistry to correlate photoreceptor-specific protein expression with visual cell disease progression. Eyes from light-adapted age-matched control andprcd-affected dogs were fixed in paraformaldehyde, embedded in diethylene glycol distearate (DGD) wax, and reacted with antibodies specific to interphotoreceptor retinoid-binding protein (IRBP), S-antigen, opsin, phosducin, γ-phosphodiesterase (γ-PDE), and β1-transducin. While IRBP expression did …
Canine Rod Transducin A-1: Cloning Of The Cdna And Evaluation Of The Gene As A Candidate For Progressive Retinal Atrophy, Kunal Ray, Victoria J. Baldwin, Caroline Zeiss, Gregory M. Acland, Gustavo D. Aguirre
Dec 1996
Canine Rod Transducin A-1: Cloning Of The Cdna And Evaluation Of The Gene As A Candidate For Progressive Retinal Atrophy, Kunal Ray, Victoria J. Baldwin, Caroline Zeiss, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: Progressive retinal atrophy (PRA) represents a heterogeneous group of retinal dystrophies, distinct forms of which occur in different canine breeds. The present study was undertaken to evaluate the gene for the a-1 subunit of the rod specific G-protein transducin (GNAT1), a member of the phototransduction pathway, as a candidate for progressive rod cone degeneration (prcd) in poodles, early retinal degeneration (erd) in elkhounds, and rod cone dysplasia 2 (rcd 2) in collies.
Methods: Oligonucleotide primers were designed from the consensus region of known cDNA sequences for GNAT1 from other species. Canine GNAT1 cDNA was cloned and sequenced after reverse …
Selective Absence Of Cone Outer Segment Β3-Transducin Immunoreactivity In Hereditary Cone Degeneration (Cd), Kathryn Gropp, A. Széll, Jun Huang, Gregory Acland, Debora Farber, Gustavo Aguirre
Aug 1996
Selective Absence Of Cone Outer Segment Β3-Transducin Immunoreactivity In Hereditary Cone Degeneration (Cd), Kathryn Gropp, A. Széll, Jun Huang, Gregory Acland, Debora Farber, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
We have used immunocytochemistry and in situ hybridization to examine the expression of photoreceptor specific genes in retinas of normal dogs and those affected with hereditary cone degeneration (cd), a rare autosomal recessive disorder that selectively affects cones. In thecdretina, cone disease begins early in life; cones are lost by extrusion of the nucleus into the inner segment, and later, by displacement of the nucleus, surrounded by a thin rim of cytoplasm, into the interphotoreceptor space. Two micrometer sections from the superior and inferior retinal meridians, extending from the optic disk to the ora serrata, were used for in situ …
Decreased Opsin Mrna And Immunoreactivity In Progressive Rod-Cone Degeneration (Prcd): Cytochemical Studies Of Early Disease And Degeneration, Jun Huang, Marie-Françoise Chesselet, Gustavo Aguirre
Dec 1993
Decreased Opsin Mrna And Immunoreactivity In Progressive Rod-Cone Degeneration (Prcd): Cytochemical Studies Of Early Disease And Degeneration, Jun Huang, Marie-Françoise Chesselet, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
Opsin mRNA level and immunoreactivity were examined by in situ hybridization and immunocytochemistry in normal and progressive rod cone degeneration (prcd)-affected dogs. In situ hybridization used 35S- and/or 3 H-labeled bovine opsin cRNA probes; immunocytochemistry used six monoclonal mouse anti-bovine opsin antibodies (MAb1) that are specific to different regions of the N-terminal, loop v-vi and the C-terminal domains. Optimal labeling and histological resolution at the single cell level were achieved with semi-thin sections of DGD wax-embedded tissues; it was possible to correlate the cytochemical observations with the disease staging in topographically defined regions that exhibited different disease severity. In early …
The Cone Matrix Sheath In The Normal And Diseased Retina: Cytochemical And Biochemical Studies Of Peanut Agglutinin-Binding Proteins In Cone And Rod-Cone Degeneration, Kenneth Long, Gustavo Aguirre
May 1991
The Cone Matrix Sheath In The Normal And Diseased Retina: Cytochemical And Biochemical Studies Of Peanut Agglutinin-Binding Proteins In Cone And Rod-Cone Degeneration, Kenneth Long, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
The fate of the cone-associated extracellular domain, or cone matrix sheath (CMS), was examined in two canine models of hereditary retinal degeneration. The diseases, which affect cones selectively (cd = cone degeneration), or rods and cones temporally (prcd = progressive rod-cone degeneration), were examined biochemically (SDS-PAGE/lectinblots) and cytochemically (light microscopy) using peanut agglutinin lectin (PNA) to selectively label this domain and associated structures. Most of the cones had disappeared in the adult cd retina. In the remaining cones, PNA labeled the ectopically located somata and the CMSs that were present around severely diseased ones. …
Β-Glucuronidase Mediated Pathway Essential For Retinal Pigment Epithelial Degradation Of Glycosaminoglycans. Disease Expression And In Vitro Disease Correction Using Retroviral Mediated Cdna Transfer, Lawrence Stramm, John Wolfe, Edward Schuchman, Mark Haskins, Donald Patterson, Gustavo Aguirre
Apr 1990
Β-Glucuronidase Mediated Pathway Essential For Retinal Pigment Epithelial Degradation Of Glycosaminoglycans. Disease Expression And In Vitro Disease Correction Using Retroviral Mediated Cdna Transfer, Lawrence Stramm, John Wolfe, Edward Schuchman, Mark Haskins, Donald Patterson, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
A β-glucuronidase mediated pathway for the degradation of glycosaminoglycans is present in the retinal pigment epithelium. The pathway has been defined using ocular tissues and cultured cells from mutant animals having a recessively inherited deficiency of the lysosomal enzyme. In situ, storage products accumulate in secondary lysosomes of the retinal pigment epithelium, the cytoplasm fills with inclusions and the cells hypertrophy; severity of the disease increases with aging. Deficient activity of β-glucuronidase is present in primary and second passage cultures. Radiolabel studies with 35SO4 show a significant retention of cell layer label by mutant retinal pigment epithelial cells …
Segregation Distortion In Inheritance Of Progressive Rod Cone Degeneration (Prcd) In Miniature Poodle Dogs, Gregory M. Acland, Susan Halloran-Blanton, Joann A. Boughman, Gustavo D. Aguirre
Feb 1990
Segregation Distortion In Inheritance Of Progressive Rod Cone Degeneration (Prcd) In Miniature Poodle Dogs, Gregory M. Acland, Susan Halloran-Blanton, Joann A. Boughman, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Segregation distortion was observed in inheritance of progressive rod–cone degeneration (prcd) in a colony of Miniature Poodle dogs. Breeding results, from both retrospective records and prospectively planned matings, were classified into five mating types: (1) affected to affected, (2) homozygous normal sire to any dam, (3) heterozygous to heterozygous, (4) heterozygous sire to affected dam, and (5) affected sire to heterozygous dam. For all but the last category, results were in accord with mendelian expectations for autosomal-recessive inheritance. However, litters of mating type 5 had fewer affected pups (20/77) than expected. The observed segregation ratio for this mating type (0.26) …
Experimental Eye Research Volume 35, Issue 6, December 1982, Pages 625–642 Cover Image Retinal Degenerations In The Dog Iii Abnormal Cyclic Nucleotide Metabolism In Rod-Cone Dysplasia, Gustavo Aguirre, Debora Farber, Richard Lolley, Paul O'Brien, James Alligood, R Fletcher
Nov 1982
Experimental Eye Research Volume 35, Issue 6, December 1982, Pages 625–642 Cover Image Retinal Degenerations In The Dog Iii Abnormal Cyclic Nucleotide Metabolism In Rod-Cone Dysplasia, Gustavo Aguirre, Debora Farber, Richard Lolley, Paul O'Brien, James Alligood, R Fletcher
Gustavo D. Aguirre, VMD, PhD
In dogs bred to develop rod-cone dysplasia, retinal development is normal until 13 days of age.Afterwards, there is an arrest of visual cell differentiation. Rod inner segments remain diminutive and outer segments fail to elongate as in controls; the outer segments show lamellar disorientation and disorganization. Affected visual cells degenerate, but the degeneration process is more rapid and extensive for rods than cones.
Cyclic GMP levels become elevated in affected retinas early during the postnatal differentiation of visual cells; this elevation precedes any morphological evidence of photoreceptor disease. Retinal protein synthesis is normal during the time that retinal cGMP levels …
