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The function of dog models in developing gene therapy strategies for human health

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Abstract

The domestic dog is of great benefit to humankind, not only through companionship and working activities cultivated through domestication and selective breeding, but also as a model for biomedical research. Many single-gene traits have been well-characterized at the genomic level, and recent advances in whole-genome association studies will allow for better understanding of complex, multigenic hereditary diseases. Additionally, the dog serves as an invaluable large animal model for assessment of novel therapeutic agents. Thus, the dog has filled a crucial step in the translation of basic research to new treatment regimens for various human diseases. Four well-characterized diseases in canine models are discussed as they relate to other animal model availability, novel therapeutic approach, and extrapolation to human gene therapy trials.

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References

  • Aartsma-Rus A, Janson AA, Kaman WE, Bremmer-Bout M, van Ommen GJ, den Dunnen JT, van Deutekom JC (2004) Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more sense. Am J Hum Genet 74:83–92

    Article  PubMed  CAS  Google Scholar 

  • Acland GM, Aguirre GD, Bennett J, Aleman TS, Cideciyan AV, Bennicelli J, Dejneka NS, Pearce-Kelling SE, Maguire AM, Palczewski K, Hauswirth WW, Jacobson SG (2005) 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. Mol Ther 12:1072–1082

    Google Scholar 

  • Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, Pearce-Kelling SE, Anand V, Zeng Y, Maguire AM, Jacobson SG, Hauswirth WW, Bennett J (2001) Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 28:92–95

    PubMed  CAS  Google Scholar 

  • Aguirre GD, Rubin LF (1974) Pathology of hemeralopia in the Alaskan malamute dog. Invest Ophthalmol 13:231–235

    PubMed  CAS  Google Scholar 

  • Aguirre GD, Rubin LF (1975) The electroretinogram in dogs with inherited cone degeneration. Invest Ophthalmol 14:840–847

    PubMed  CAS  Google Scholar 

  • Aguirre GD, Baldwin V, Pearce-Kelling S, Narfstrom K, Ray K, Acland GM (1998) Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect. Mol Vis 4:23

    PubMed  CAS  Google Scholar 

  • Amado D, Mingozzi F, Hui D, Bennicelli JL, Wei Z, Chen Y, Bote E, Grant RL, Golden JA, Narfstrom K, Syed NA, Orlin SE, High KA, Maguire AM, Bennett J (2010) Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness. Sci Transl Med 2:21ra16

    PubMed  Google Scholar 

  • Anderson DC, Springer TA (1987) Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150, 95 glycoproteins. Annu Rev Med 38:175–194

    Article  PubMed  CAS  Google Scholar 

  • Anderson DC, Schmalsteig FC, Finegold MJ, Hughes BJ, Rothlein R, Miller LJ, Kohl S, Tosi MF, Jacobs RL, Waldrop TC, Goldman AS, Shearer WT, Springer TA (1985) The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J Infect Dis 152:668–689

    Article  PubMed  CAS  Google Scholar 

  • Arnaout MA (1990) Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood 75:1037–1050

    PubMed  CAS  Google Scholar 

  • Arnaout MA, Dana N, Gupta SK, Tenen DG, Fathallah DM (1990) Point mutations impairing cell surface expression of the common beta subunit (CD18) in a patient with leukocyte adhesion molecule (Leu-CAM) deficiency. J Clin Invest 85:977–981

    Article  PubMed  CAS  Google Scholar 

  • Axelrod JH, Read MS, Brinkhous KM, Verma IM (1990) Phenotypic correction of factor IX deficiency in skin fibroblasts of hemophilic dogs. Proc Nl Acad Sci USA 87:5173–5177

    Article  CAS  Google Scholar 

  • Bauer TR Jr, Hickstein DD (2000) Gene therapy for leukocyte adhesion deficiency. Curr Opin Mol Ther 2:383–388

    PubMed  CAS  Google Scholar 

  • Bauer TR Jr, Creevy KE, Gu YC, Tuschong LM, Donahue RE, Metzger ME, Embree LJ, Burkholder T, Bacher JD, Romines C, Thomas ML 3rd, Colenda L, Hickstein DD (2004a) Very low levels of donor CD18+ neutrophils following allogeneic hematopoietic stem cell transplantation reverse the disease phenotype in canine leukocyte adhesion deficiency. Blood 103:3582–3589

    Article  PubMed  CAS  Google Scholar 

  • Bauer TR Jr, Gu YC, Creevy KE, Tuschong LM, Embree L, Holland SM, Sokolic RA, Hickstein DD (2004b) Leukocyte adhesion deficiency in children and Irish setter dogs. Pediatr Res 55:363–367

    Article  PubMed  Google Scholar 

  • Bauer TR Jr, Allen JM, Hai M, Tuschong LM, Khan IF, Olson EM, Adler RL, Burkholder TH, Gu YC, Russell DW, Hickstein DD (2008) Successful treatment of canine leukocyte adhesion deficiency by foamy virus vectors. Nat Med 14:93–97

    Article  PubMed  CAS  Google Scholar 

  • Bauer TR Jr, Olson EM, Huo Y, Tuschong LM, Allen JM, Li Y, Burkholder TH, Russell DW (2011) Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter. Gene Ther 18(6):553–559

    Article  PubMed  CAS  Google Scholar 

  • Bulfield G, Siller WG, Wight PA, Moore KJ (1984) X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci USA 81:1189–1192

    Article  PubMed  CAS  Google Scholar 

  • Cai X, Conley SM, Naash MI (2009) RPE65: role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet 30:57–62

    Article  PubMed  CAS  Google Scholar 

  • Campbell KP (1995) Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. Cell 80:675–679

    Article  PubMed  CAS  Google Scholar 

  • Cooper BJ, Winand NJ, Stedman H, Valentine BA, Hoffman EP, Kunkel LM, Scott MO, Fischbeck KH, Kornegay JN, Avery RJ (1988) The homologue of the Duchenne locus is defective in X-linked muscular dystrophy of dogs. Nature 334:154–156

    Article  PubMed  CAS  Google Scholar 

  • Creevy KE, Bauer TR Jr, Tuschong LM, Embree LJ, Silverstone AM, Bacher JD, Romines C, Garnier J, Thomas ML III, Colenda L, Hickstein DD (2003) Mixed chimeric hematopoietic stem cell transplant reverses the disease phenotype in canine leukocyte adhesion deficiency. Vet Immunol Immunopathol 95:113–121

    Article  PubMed  CAS  Google Scholar 

  • Crowley CA, Curnutte JT, Rosin RE, Andre-Schwartz J, Gallin JI, Klempner M, Snyderman R, Southwick FS, Stossel TP, Babior BM (1980) An inherited abnormality of neutrophil adhesion. Its genetic transmission and its association with a missing protein. N Engl J Med 302:1163–1168

    Article  PubMed  CAS  Google Scholar 

  • Dalkilic I, Kunkel LM (2003) Muscular dystrophies: genes to pathogenesis. Curr Opin Genet Dev 13:231–238

    Article  PubMed  CAS  Google Scholar 

  • den Hollander AI, Roepman R, Koenekoop RK, Cremers FP (2008) Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res 27:391–419

    Article  CAS  Google Scholar 

  • den Hollander AI, Black A, Bennett J, Cremers FP (2010) Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies. J Clin Invest 120:3042–3053

    Article  CAS  Google Scholar 

  • Ding XQ, Harry CS, Umino Y, Matveev AV, Fliesler SJ, Barlow RB (2009) Impaired cone function and cone degeneration resulting from CNGB3 deficiency: down-regulation of CNGA3 biosynthesis as a potential mechanism. Hum Mol Genet 18:4770–4780

    Article  PubMed  CAS  Google Scholar 

  • Ellinwood NM, Ausseil J, Desmaris N, Bigou S, Liu S, Jens JK, Snella EM, Mohammed EE, Thomson CB, Raoul S, Joussemet B, Roux F, Cherel Y, Lajat Y, Piraud M, Benchaouir R, Hermening S, Petry H, Froissart R, Tardieu M, Ciron C, Moullier P, Parkes J, Kline KL, Maire I, Vanier MT, Heard JM, Colle MA (2011) Safe, efficient, and reproducible gene therapy of the brain in the dog models of Sanfilippo and Hurler syndromes. Mol Ther 19:251–259

    Article  PubMed  CAS  Google Scholar 

  • Emery AE (2002) The muscular dystrophies. Lancet 359:687–695

    Article  PubMed  CAS  Google Scholar 

  • Finocchiaro LM, Villaverde MS, Gil-Cardeza ML, Riveros MD, Glikin GC (2011) Cytokine-enhanced vaccine and interferon-beta plus suicide gene as combined therapy for spontaneous canine sarcomas. Res Vet Sci. doi:10.1016/j.rvsc.2010.12.012

  • Fletcher S, Honeyman K, Fall AM, Harding PL, Johnsen RD, Wilton SD (2006) Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide. J Gene Med 8:207–216

    Article  PubMed  CAS  Google Scholar 

  • Galibert F, Andre C (2006) The dog genome. Genome Dyn 2:46–59

    Article  PubMed  CAS  Google Scholar 

  • Gerstner A, Zong X, Hofmann F, Biel M (2000) Molecular cloning and functional characterization of a new modulatory cyclic nucleotide-gated channel subunit from mouse retina. J Neurosci 20:1324–1332

    PubMed  CAS  Google Scholar 

  • Giger U, Boxer LA, Simpson PJ, Lucchesi BR, Todd RF III (1987) Deficiency of leukocyte surface glycoproteins Mo1, LFA-1, and Leu M5 in a dog with recurrent bacterial infections: an animal model. Blood 69:1622–1630

    PubMed  CAS  Google Scholar 

  • Grady RM, Teng H, Nichol MC, Cunningham JC, Wilkinson RS, Sanes JR (1997) Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy. Cell 90:729–738

    Article  PubMed  CAS  Google Scholar 

  • Gregorevic P, Blankinship MJ, Allen JM, Chamberlain JS (2008) Systemic microdystrophin gene delivery improves skeletal muscle structure and function in old dystrophic mdx mice. Mol Ther 16:657–664

    Article  PubMed  CAS  Google Scholar 

  • Gropp KE, Szel A, Huang JC, Acland GM, Farber DB, Aguirre GD (1996) Selective absence of cone outer segment beta 3-transducin immunoreactivity in hereditary cone degeneration (cd). Exp Eye Res 63:285–296

    Article  PubMed  CAS  Google Scholar 

  • Hajitou A (2010) Targeted systemic gene therapy and molecular imaging of cancer contribution of the vascular-targeted AAVP vector. Adv Genet 69:65–82

    Article  PubMed  CAS  Google Scholar 

  • Haskins ME, Giger U, Patterson DF (2006) Animal models of lysosomal storage diseases: their development and clinical relevance. In: Mehta A, Beck M, Sunder-Plassmann G (eds) Fabry disease: perspectives from 5 years of FOS. Oxford PharmaGenesis, Oxford

    Google Scholar 

  • Hoffman EP, Brown RH Jr, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919–928

    Article  PubMed  CAS  Google Scholar 

  • Howell JM (1999) Is there a future for gene therapy? Neuromuscul Disord 9:102–107

    Article  PubMed  CAS  Google Scholar 

  • Hunter MJ, Tuschong LM, Fowler CJ, Bauer TR Jr, Burkholder TH, Hickstein DD (2011) Gene therapy of canine leukocyte adhesion deficiency using lentiviral vectors with human CD11b and CD18 promoters driving canine CD18 expression. Mol Ther 19:113–121

    Article  PubMed  CAS  Google Scholar 

  • Jearawiriyapaisarn N, Moulton HM, Buckley B, Roberts J, Sazani P, Fucharoen S, Iversen PL, Kole R (2008) Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx mice. Mol Ther 16:1624–1629

    Article  PubMed  CAS  Google Scholar 

  • Kay MA, Landen CN, Rothenberg SR, Taylor LA, Leland F, Wiehle S, Fang B, Bellinger D, Finegold M, Thompson AR (1994) In vivo hepatic gene therapy: complete albeit transient correction of factor IX deficiency in hemophilia B dogs. Proc Natl Acad Sci USA 91:2353–2357

    Article  PubMed  CAS  Google Scholar 

  • Kehrli ME Jr, Ackermann MR, Shuster DE, van der Maaten MJ, Schmalstieg FC, Anderson DC, Hughes BJ (1992) Bovine leukocyte adhesion deficiency. Beta 2 integrin deficiency in young Holstein cattle. Am J Pathol 140:1489–1492

    PubMed  Google Scholar 

  • Kijas JM, Juneja RK, Gafvert S, Andersson L (2000) Detection of the causal mutation for canine leukocyte adhesion deficiency (CLAD) using pyrosequencing. Anim Genet 31:326–328

    Article  PubMed  CAS  Google Scholar 

  • Kinali M, Arechavala-Gomeza V, Feng L, Cirak S, Hunt D, Adkin C, Guglieri M, Ashton E, Abbs S, Nihoyannopoulos P, Garralda ME, Rutherford M, McCulley C, Popplewell L, Graham IR, Dickson G, Wood MJ, Wells DJ, Wilton SD, Kole R, Straub V, Bushby K, Sewry C, Morgan JE, Muntoni F (2009) Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol 8:918–928

    Article  PubMed  CAS  Google Scholar 

  • Kishnani PS, Bao Y, Wu JY, Brix AE, Lin JL, Chen YT (1997) Isolation and nucleotide sequence of canine glucose-6-phosphatase mRNA: identification of mutation in puppies with glycogen storage disease type Ia. Biochem Mol Med 61:168–177

    Article  PubMed  CAS  Google Scholar 

  • Kishnani PS, Faulkner E, VanCamp S, Jackson M, Brown T, Boney A, Koeberl D, Chen YT (2001) Canine model and genomic structural organization of glycogen storage disease type Ia (GSD Ia). Vet Pathol 38:83–91

    Article  PubMed  CAS  Google Scholar 

  • Koeberl DD, Pinto C, Sun B, Li S, Kozink DM, Benjamin DK Jr, Demaster AK, Kruse MA, Vaughn V, Hillman S, Bird A, Jackson M, Brown T, Kishnani PS, Chen YT (2008) AAV vector-mediated reversal of hypoglycemia in canine and murine glycogen storage disease type Ia. Mol Ther 16:665–672

    Article  PubMed  CAS  Google Scholar 

  • Koeberl DD, Pinto C, Brown T, Chen YT (2009) Gene therapy for inherited metabolic disorders in companion animals. ILAR J 50:122–127

    PubMed  CAS  Google Scholar 

  • Kohl S, Baumann B, Broghammer M, Jagle H, Sieving P, Kellner U, Spegal R, Anastasi M, Zrenner E, Sharpe LT, Wissinger B (2000) Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum Mol Genet 9:2107–2116

    Article  PubMed  CAS  Google Scholar 

  • Kohl S, Varsanyi B, Antunes GA, Baumann B, Hoyng CB, Jagle H, Rosenberg T, Kellner U, Lorenz B, Salati R, Jurklies B, Farkas A, Andreasson S, Weleber RG, Jacobson SG, Rudolph G, Castellan C, Dollfus H, Legius E, Anastasi M, Bitoun P, Lev D, Sieving PA, Munier FL, Zrenner E, Sharpe LT, Cremers FP, Wissinger B (2005) CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. Eur J Hum Genet 13:302–308

    Article  PubMed  CAS  Google Scholar 

  • Komaromy AM, Alexander JJ, Cooper AE, Chiodo VA, Glushakova LG, Acland GM, Hauswirth WW, Aguirre GD (2008) Targeting gene expression to cones with human cone opsin promoters in recombinant AAV. Gene Ther 15:1049–1055

    Article  PubMed  CAS  Google Scholar 

  • Komaromy AM, Alexander JJ, Rowlan JS, Garcia MM, Chiodo VA, Kaya A, Tanaka JC, Acland GM, Hauswirth WW, Aguirre GD (2010) Gene therapy rescues cone function in congenital achromatopsia. Hum Mol Genet 19:2581–2593

    Article  PubMed  CAS  Google Scholar 

  • Kornegay JN, Tuler SM, Miller DM, Levesque DC (1988) Muscular dystrophy in a litter of golden retriever dogs. Muscle Nerve 11:1056–1064

    Article  PubMed  CAS  Google Scholar 

  • Kornegay JN, Li J, Bogan JR, Bogan DJ, Chen C, Zheng H, Wang B, Qiao C, Howard JF Jr, Xiao X (2010) Widespread muscle expression of an AAV9 human mini-dystrophin vector after intravenous injection in neonatal dystrophin-deficient dogs. Mol Ther 18:1501–1508

    Article  PubMed  CAS  Google Scholar 

  • Kwok WW, Schuening F, Stead RB, Miller AD (1986) Retroviral transfer of genes into canine hemopoietic progenitor cells in culture: a model for human gene therapy. Proc Natl Acad Sci USA 83:4552–4555

    Article  PubMed  CAS  Google Scholar 

  • Lheriteau E, Libeau L, Stieger K, Deschamps JY, Mendes-Madeira A, Provost N, Lemoine F, Mellersh C, Ellinwood NM, Cherel Y, Moullier P, Rolling F (2009) The RPGRIP1-deficient dog, a promising canine model for gene therapy. Mol Vis 15:349–361

    PubMed  CAS  Google Scholar 

  • Lu QL, Rabinowitz A, Chen YC, Yokota T, Yin H, Alter J, Jadoon A, Bou-Gharios G, Partridge T (2005) Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc Natl Acad Sci USA 102:198–203

    Article  PubMed  CAS  Google Scholar 

  • Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell’Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J (2008) Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med 358:2240–2248

    Article  PubMed  CAS  Google Scholar 

  • Malech HL, Hickstein DD (2007) Genetics, biology and clinical management of myeloid cell primary immune deficiencies: chronic granulomatous disease and leukocyte adhesion deficiency. Curr Opin Hematol 14:29–36

    Article  PubMed  Google Scholar 

  • Mango RL, Xu L, Sands MS, Vogler C, Seiler G, Schwarz T, Haskins ME, Ponder KP (2004) Neonatal retroviral vector-mediated hepatic gene therapy reduces bone, joint, and cartilage disease in mucopolysaccharidosis VII mice and dogs. Mol Genet Metab 82:4–19

    Article  PubMed  CAS  Google Scholar 

  • Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt P, Konkle B, Dake M, Kaye R, Razavi M, Zajko A, Zehnder J, Rustagi PK, Nakai H, Chew A, Leonard D, Wright JF, Lessard RR, Sommer JM, Tigges M, Sabatino D, Luk A, Jiang H, Mingozzi F, Couto L, Ertl HC, High KA, Kay MA (2006) Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med 12:342–347

    Article  PubMed  CAS  Google Scholar 

  • Margaritis P (2010) Long-term expression of canine FVIIa in hemophilic dogs. Thromb Res 125 Suppl 1:S60–S62

    Article  PubMed  CAS  Google Scholar 

  • Marlhens F, Bareil C, Griffoin JM, Zrenner E, Amalric P, Eliaou C, Liu SY, Harris E, Redmond TM, Arnaud B, Claustres M, Hamel CP (1997) Mutations in RPE65 cause Leber’s congenital amaurosis. Nat Genet 17:139–141

    Article  PubMed  CAS  Google Scholar 

  • Michaelides M, Hunt DM, Moore AT (2004) The cone dysfunction syndromes. Br J Ophthalmol 88:291–297

    Article  PubMed  CAS  Google Scholar 

  • Michaelides M, Hardcastle AJ, Hunt DM, Moore AT (2006) Progressive cone and cone-rod dystrophies: phenotypes and underlying molecular genetic basis. Surv Ophthalmol 51:232–258

    Article  PubMed  Google Scholar 

  • Milunsky A, Huang XL, Milunsky J, DeStefano A, Baldwin CT (1999) A locus for autosomal recessive achromatopsia on human chromosome 8q. Clin Genet 56:82–85

    Article  PubMed  CAS  Google Scholar 

  • Nakamura A, Takeda S (2011) Mammalian models of Duchenne muscular dystrophy: pathological characteristics and therapeutic applications. J Biomed Biotechnol 2011:184393

    Article  PubMed  Google Scholar 

  • Narfstrom K, Wrigstad A, Nilsson SE (1989) The Briard dog: a new animal model of congenital stationary night blindness. Br J Ophthalmol 73:750–756

    Article  PubMed  CAS  Google Scholar 

  • Nayak S, Herzog RW (2010) Progress and prospects: immune responses to viral vectors. Gene Ther 17:295–304

    Article  PubMed  CAS  Google Scholar 

  • Nelson EJ, Tuschong LM, Hunter MJ, Bauer TR Jr, Burkholder TH, Hickstein DD (2010) Lentiviral vectors incorporating a human elongation factor 1alpha promoter for the treatment of canine leukocyte adhesion deficiency. Gene Ther 17:672–677

    Article  PubMed  CAS  Google Scholar 

  • Nguyen F, Cherel Y, Guigand L, Goubault-Leroux I, Wyers M (2002) Muscle lesions associated with dystrophin deficiency in neonatal golden retriever puppies. J Comp Pathol 126:100–108

    Article  PubMed  CAS  Google Scholar 

  • Nichols TC, Dillow AM, Franck HW, Merricks EP, Raymer RA, Bellinger DA, Arruda VR, High KA (2009) Protein replacement therapy and gene transfer in canine models of hemophilia A, hemophilia B, von Willebrand disease, and factor VII deficiency. ILAR J 50:144–167

    PubMed  CAS  Google Scholar 

  • Nicoletti A, Wong DJ, Kawase K, Gibson LH, Yang-Feng TL, Richards JE, Thompson DA (1995) Molecular characterization of the human gene encoding an abundant 61 kDa protein specific to the retinal pigment epithelium. Hum Mol Genet 4:641–649

    Article  PubMed  CAS  Google Scholar 

  • Novelli EM, Barranger JA (2001) Gene therapy for lysosomal storage disorders. Expert Opin Biol Ther 1:857–867

    Article  PubMed  CAS  Google Scholar 

  • Ohshima S, Shin J, Yuasa K, Nishiyama A, Kira J, Okada T, Takeda S (2008) Transduction efficiency and immune response associated with the administration of AAV8 vector into dog skeletal muscle. Mol Ther 17:73–80

    Article  PubMed  CAS  Google Scholar 

  • Oshima J, Magner DB, Lee JA, Breman AM, Schmitt ES, White LD, Crowe CA, Merrill M, Jayakar P, Rajadhyaksha A, Eng CM, del Gaudio D (2009) Regional genomic instability predisposes to complex dystrophin gene rearrangements. Hum Genet 126:411–423

    Article  PubMed  Google Scholar 

  • Ostrander EA, Kruglyak L (2000) Unleashing the canine genome. Genome Res 10:1271–1274

    Article  PubMed  CAS  Google Scholar 

  • Ostrander EA, Wayne RK (2005) The canine genome. Genome Res 15:1706–1716

    Article  PubMed  CAS  Google Scholar 

  • Parker HG, Ostrander EA (2005) Canine genomics and genetics: running with the pack. PLoS Genet 1:e58

    Article  PubMed  CAS  Google Scholar 

  • Parker HG, Shearin AL, Ostrander EA (2010) Man’s best friend becomes biology’s best in show: genome analyses in the domestic dog. Annu Rev Genet 44:309–336

    Article  PubMed  CAS  Google Scholar 

  • Pastoret C, Sebille A (1995) mdx mice show progressive weakness and muscle deterioration with age. J Neurol Sci 129:97–105

    Article  PubMed  CAS  Google Scholar 

  • Patterson DF, Haskins ME, Jezyk PF, Giger U, Meyers-Wallen VN, Aguirre G, Fyfe JC, Wolfe JH (1988) Research on genetic diseases: reciprocal benefits to animals and man. J Am Vet Med Assoc 193:1131–1144

    PubMed  CAS  Google Scholar 

  • Perrault I, Rozet JM, Gerber S, Ghazi I, Leowski C, Ducroq D, Souied E, Dufier JL, Munnich A, Kaplan J (1999) Leber congenital amaurosis. Mol Genet Metab 68:200–208

    Article  PubMed  CAS  Google Scholar 

  • Pichavant C, Chapdelaine P, Cerri DG, Dominique JC, Quenneville SP, Skuk D, Kornegay JN, Bizario JC, Xiao X, Tremblay JP (2010) Expression of dog microdystrophin in mouse and dog muscles by gene therapy. Mol Ther 18:1002–1009

    Article  PubMed  CAS  Google Scholar 

  • Pluhar GE, Grogan PT, Seiler C, Goulart M, SantaCruz KS, Carlson C, Chen W, Olin MR, Lowenstein PR, Castro MG, Haines SJ, Ohlfest JR (2010) Anti-tumor immune response correlates with neurological symptoms in a dog with spontaneous astrocytoma treated by gene and vaccine therapy. Vaccine 28:3371–3378

    Article  PubMed  CAS  Google Scholar 

  • Powell JS, Ragni MV, White GC II, Lusher JM, Hillman-Wiseman C, Moon TE, Cole V, Ramanathan-Girish S, Roehl H, Sajjadi N, Jolly DJ, Hurst D (2003) Phase I trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion. Blood 102:2038–2045

    Article  PubMed  CAS  Google Scholar 

  • Redmond TM, Yu S, Lee E, Bok D, Hamasaki D, Chen N, Goletz P, Ma JX, Crouch RK, Pfeifer K (1998) Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle. Nat Genet 20:344–351

    Article  PubMed  CAS  Google Scholar 

  • Reed SD, Fulmer A, Buckholz J, Zhang B, Cutrera J, Shiomitsu K, Li S (2010) Bleomycin/interleukin-12 electrochemogenetherapy for treating naturally occurring spontaneous neoplasms in dogs. Cancer Gene Ther 17:571–578

    Article  PubMed  CAS  Google Scholar 

  • Renshaw HW, Chatburn C, Bryan GM, Bartsch RC, Davis WC (1975) Canine granulocytopathy syndrome: neutrophil dysfunction in a dog with recurrent infections. J Am Vet Med Assoc 166:443–447

    PubMed  CAS  Google Scholar 

  • Rosenberg T, Baumann B, Kohl S, Zrenner E, Jorgensen AL, Wissinger B (2004) Variant phenotypes of incomplete achromatopsia in two cousins with GNAT2 gene mutations. Invest Ophthalmol Vis Sci 45:4256–4262

    Article  PubMed  Google Scholar 

  • Rubin LF, Bourns TK, Lord LH (1967) Hemeralopia in dogs: heredity of hemeralopia in Alaskan Malamutes. Am J Vet Res 28:355–357

    PubMed  CAS  Google Scholar 

  • Saito T, Nakamura A, Aoki Y, Yokota T, Okada T, Osawa M, Takeda S (2010) Antisense PMO found in dystrophic dog model was effective in cells from exon 7-deleted DMD patient. PLoS One 5:e12239

    Article  PubMed  CAS  Google Scholar 

  • Scharffetter-Kochanek K, Lu H, Norman K, van Nood N, Munoz F, Grabbe S, McArthur M, Lorenzo I, Kaplan S, Ley K, Wayne Smith C, Montgomery CA, Rich S, Beaudet AL (1998) Spontaneous skin ulceration and defective T cell function in CD18 null mice. J Exp Med 188:119–131

    Article  PubMed  CAS  Google Scholar 

  • Sharp NJ, Kornegay JN, Van Camp SD, Herbstreith MH, Secore SL, Kettle S, Hung WY, Constantinou CD, Dykstra MJ, Roses AD (1992) An error in dystrophin mRNA processing in golden retriever muscular dystrophy, an animal homologue of Duchenne muscular dystrophy. Genomics 13:115–121

    Article  PubMed  CAS  Google Scholar 

  • Shearin AL, Ostrander EA (2010) Leading the way: canine models of genomics and disease. Dis Model Mech 3:27–34

    Article  PubMed  CAS  Google Scholar 

  • Shimatsu Y, Katagiri K, Furuta T, Nakura M, Tanioka Y, Yuasa K, Tomohiro M, Kornegay JN, Nonaka I, Takeda S (2003) Canine X-linked muscular dystrophy in Japan (CXMDJ). Exp Anim 52:93–97

    Article  PubMed  CAS  Google Scholar 

  • Shuster DE, Kehrli ME, Ackermann MR, Gilbert RO (1992) Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle. Proc Natl Acad Sci USA 89:9225–9229

    Article  PubMed  CAS  Google Scholar 

  • Sicinski P, Geng Y, Ryder-Cook AS, Barnard EA, Darlison MG, Barnard PJ (1989) The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 244:1578–1580

    Article  PubMed  CAS  Google Scholar 

  • Sidjanin DJ, Lowe JK, McElwee JL, Milne BS, Phippen TM, Sargan DR, Aguirre GD, Acland GM, Ostrander EA (2002) Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Hum Mol Genet 11:1823–1833

    Article  PubMed  CAS  Google Scholar 

  • Sokolic R, Kesserwan C, Candotti F (2008) Recent advances in gene therapy for severe congenital immunodeficiency diseases. Curr Opin Hematol 15:375–380

    Article  PubMed  CAS  Google Scholar 

  • Spady TC, Ostrander EA (2008) Canine behavioral genetics: pointing out the phenotypes and herding up the genes. Am J Hum Genet 82:10–18

    Article  PubMed  CAS  Google Scholar 

  • Sutter NB, Ostrander EA (2004) Dog star rising: the canine genetic system. Nat Rev Genet 5:900–910

    Article  PubMed  CAS  Google Scholar 

  • Switonski M, Szczerbal I, Nowacka J (2004) The dog genome map and its use in mammalian comparative genomics. J Appl Genet 45:195–214

    PubMed  Google Scholar 

  • Thamm DH, Kurzman ID, Clark MA, Ehrhart EJ III, Kraft SL, Gustafson DL, Vail DM (2010) Preclinical investigation of PEGylated tumor necrosis factor alpha in dogs with spontaneous tumors: phase I evaluation. Clin Cancer Res 16:1498–1508

    Article  PubMed  CAS  Google Scholar 

  • Thiadens AA, den Hollander AI, Roosing S, Nabuurs SB, Zekveld-Vroon RC, Collin RW, De Baere E, Koenekoop RK, van Schooneveld MJ, Strom TM, van Lith-Verhoeven JJ, Lotery AJ, van Moll-Ramirez N, Leroy BP, van den Born LI, Hoyng CB, Cremers FP, Klaver CC (2009) Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders. Am J Hum Genet 85:240–247

    Article  PubMed  CAS  Google Scholar 

  • Thomas C, Le Deist F, Cavazzana-Calvo M, Benkerrou M, Haddad E, Blanche S, Hartmann W, Friedrich W, Fischer A (1995) Results of allogeneic bone marrow transplantation in patients with leukocyte adhesion deficiency. Blood 86:1629–1635

    PubMed  CAS  Google Scholar 

  • Traas AM, Wang P, Ma X, Tittiger M, Schaller L, O’donnell P, Sleeper MM, Vite C, Herati R, Aguirre GD, Haskins M, Ponder KP (2007) Correction of clinical manifestations of canine mucopolysaccharidosis I with neonatal retroviral vector gene therapy. Mol Ther 15:1423–1431

    Article  PubMed  CAS  Google Scholar 

  • Trowald-Wigh G, Hakansson L, Johannisson A, Norrgren L, Hard af Segerstad C (1992) Leucocyte adhesion protein deficiency in Irish setter dogs. Vet Immunol Immunopathol 32:261–280

    Article  PubMed  CAS  Google Scholar 

  • Tsai KL, Clark LA, Murphy KE (2007) Understanding hereditary diseases using the dog and human as companion model systems. Mamm Genome 18:444–451

    Article  PubMed  Google Scholar 

  • van Deutekom JC (2005) Gene therapy: the ‘pro-sense’ approach to Duchenne muscular dystrophy. Eur J Hum Genet 13:518–519

    Article  PubMed  CAS  Google Scholar 

  • Veske A, Nilsson SE, Narfstrom K, Gal A (1999) Retinal dystrophy of Swedish briard/briard-beagle dogs is due to a 4-bp deletion in RPE65. Genomics 57:57–61

    Article  PubMed  CAS  Google Scholar 

  • Walmsley GL, Arechavala-Gomeza V, Fernandez-Fuente M, Burke MM, Nagel N, Holder A, Stanley R, Chandler K, Marks SL, Muntoni F, Shelton GD, Piercy RJ (2010) A Duchenne muscular dystrophy gene hot spot mutation in dystrophin-deficient Cavalier King Charles spaniels is amenable to exon 51 skipping. PLoS One 5:e8647

    Article  PubMed  CAS  Google Scholar 

  • Wang B, O’Malley TM, Xu L, Vite C, Wang P, O’Donnell PA, Ellinwood NM, Haskins ME, Ponder KP (2006) Expression in blood cells may contribute to biochemical and pathological improvements after neonatal intravenous gene therapy for mucopolysaccharidosis VII in dogs. Mol Genet Metab 87:8–21

    Article  PubMed  CAS  Google Scholar 

  • Wang B, Li J, Fu FH, Xiao X (2009) Systemic human minidystrophin gene transfer improves functions and life span of dystrophin and dystrophin/utrophin-deficient mice. J Orthop Res 27:421–426

    Article  PubMed  Google Scholar 

  • Watchko J, O’Day T, Wang B, Zhou L, Tang Y, Li J, Xiao X (2002) Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice. Hum Gene Ther 13:1451–1460

    Article  PubMed  CAS  Google Scholar 

  • Weinstein DA, Correia CE, Conlon T, Specht A, Verstegen J, Onclin-Verstegen K, Campbell-Thompson M, Dhaliwal G, Mirian L, Cossette H, Falk DJ, Germain S, Clement N, Porvasnik S, Fiske L, Struck M, Ramirez HE, Jordan J, Andrutis K, Chou JY, Byrne BJ, Mah CS (2010) Adeno-associated virus-mediated correction of a canine model of glycogen storage disease type Ia. Hum Gene Ther 21:903–910

    Article  PubMed  CAS  Google Scholar 

  • Wissinger B, Jagle H, Kohl S, Broghammer M, Baumann B, Hanna DB, Hedels C, Apfelstedt-Sylla E, Randazzo G, Jacobson SG, Zrenner E, Sharpe LT (1998) Human rod monochromacy: linkage analysis and mapping of a cone photoreceptor expressed candidate gene on chromosome 2q11. Genomics 51:325–331

    Article  PubMed  CAS  Google Scholar 

  • Wiszniewski W, Lewis RA, Lupski JR (2007) Achromatopsia: the CNGB3 p.T383fsX mutation results from a founder effect and is responsible for the visual phenotype in the original report of uniparental disomy 14. Hum Genet 121:433–439

    Article  PubMed  CAS  Google Scholar 

  • Xu L, Haskins ME, Melniczek JR, Gao C, Weil MA, O’Malley TM, O’Donnell PA, Mazrier H, Ellinwood NM, Zweigle J, Wolfe JH, Ponder KP (2002) Transduction of hepatocytes after neonatal delivery of a Moloney murine leukemia virus based retroviral vector results in long-term expression of beta-glucuronidase in mucopolysaccharidosis VII dogs. Mol Ther 5:141–153

    Article  PubMed  CAS  Google Scholar 

  • Xu L, Gao C, Sands MS, Cai S, Nichols TC, Bellinger DA, Raymer RA, McCorquoldale S, Ponder KP (2003) Neonatal or hepatocyte growth factor-potentiated adult gene therapy with a retroviral vector results in therapeutic levels of canine factor IX for hemophilia B. Blood 101:3924–3932

    Article  PubMed  CAS  Google Scholar 

  • Yokota T, Lu Q, Partridge T, Kobayashi M, Nakamura A, Takeda S, Hoffman E (2009) Efficacy of systemic morpholino exon-skipping in duchenne dystrophy dogs. Ann Neurol 65:667–676

    Article  PubMed  Google Scholar 

  • Yoshimura M, Sakamoto M, Ikemoto M, Mochizuki Y, Yuasa K, Miyagoe-Suzuki Y, Takeda S (2004) AAV vector-mediated microdystrophin expression in a relatively small percentage of mdx myofibers improved the mdx phenotype. Mol Ther 10:821–828

    Article  PubMed  CAS  Google Scholar 

  • Yue Y, Liu M, Duan D (2006) C-terminal-truncated microdystrophin recruits dystrobrevin and syntrophin to the dystrophin-associated glycoprotein complex and reduces muscular dystrophy in symptomatic utrophin/dystrophin double-knockout mice. Mol Ther 14:79–87

    Article  PubMed  CAS  Google Scholar 

  • Zufferey R, Dull T, Mandel RJ, Bukovsky A, Quiroz D, Naldini L, Trono D (1998) Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 72:9873–9880

    PubMed  CAS  Google Scholar 

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Nowend, K.L., Starr-Moss, A.N. & Murphy, K.E. The function of dog models in developing gene therapy strategies for human health. Mamm Genome 22, 476–485 (2011). https://doi.org/10.1007/s00335-011-9348-0

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