Advertisement

RPGRIP1 and Cone–Rod Dystrophy in Dogs

  • Tatyana KuznetsovaEmail author
  • Barbara Zangerl
  • Gustavo D. Aguirre
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

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.

Keywords

RPGRIP1 Polymorphism Cone–rod dystrophy Protein network Photoreceptor cilia 

Notes

Acknowledgments

This study was supported by Morris Animal Foundation, EY-06855, 17549, Foundation Fighting Blindness Center Grant, and Van Sloun Fund

References

  1. Aguirre GD, Acland GM (2006) Models Mutants and Man: Searching for Unique Phenotypes and Genes in the Dog Model of Inherited Retinal Degeneration. The Dog and Its Genome. In: Ostrander EA, Giger U, Lindblad-Toh K (eds). Cold Spring Harbor, NY, Cold Spring Harbor Laboratory Press: 291325Google Scholar
  2. Castagnet P, Mavlyutov T, Cai Y et al (2003) RPGRIP1s with distinct neuronal localization and biochemical properties associate selectively with RanBP2 in amacrine neurons. Hum Mol Genet 12:1847–1863PubMedCrossRefGoogle Scholar
  3. Dryja TP, Adams SM, Grimsby JL et al (2001) Null RPGRIP1 alleles in patients with Leber congenital amaurosis. Am J Hum Genet 68:1295–1298PubMedCrossRefGoogle Scholar
  4. Eley L, Gabrielides C, Adams M et al (2008) Jouberin localizes to collecting ducts and interacts with nephrocystin-1. Kidney Int 74:1139–1149PubMedCrossRefGoogle Scholar
  5. Goldstein O, Mezey JG, Boyko AR et al (2010) ADAM9 mutation in Canine Cone-Rod Dystrophy 3 (crd3) establishes homology with human CORD9. Mol Vis 16:1549–1569PubMedGoogle Scholar
  6. Hameed A, Abid A, Aziz A et al (2003) Evidence of RPGRIP1 gene mutations associated with recessive cone-rod dystrophy. J Med Genet 40:616–619PubMedCrossRefGoogle Scholar
  7. Khanna H, Hurd TW, Lillo C et al (2005) RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins. J Biol Chem 280:33580–33587PubMedCrossRefGoogle Scholar
  8. Kijas JW, Zangerl B, Miller B et al (2004) Cloning of the canine ABCA4 gene and evaluation in canine cone-rod dystrophies and progressive retinal atrophies. Mol Vis 10:223–232PubMedGoogle Scholar
  9. Kim J, Krishnaswami SR, Gleeson JG (2008) CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium. Hum Mol Genet 17:3796–3805PubMedCrossRefGoogle Scholar
  10. Kuznetsova T, Zangerl B, Goldstein O et al (2011) Structural organization and expression pattern of the canine RPGRIP1 isoforms in retinal tissue. Invest Ophthalmol Vis Sci 52:2989–2998Google Scholar
  11. Linari M, Ueffing M, Manson F et al (1999) The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase. Proc Natl Acad Sci USA 96:1315–1320PubMedCrossRefGoogle Scholar
  12. Mavlyutov TA, Zhao H, Ferreira PA (2002) Species-specific subcellular localization of RPGR and RPGRIP isoforms: Implications for the phenotypic variability of congenital retinopathies among species. Hum Mol Genet 11:1899–1907PubMedCrossRefGoogle Scholar
  13. Mellersh CS, Boursnell ME, Pettitt L et al (2006) Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics 88:293–301PubMedCrossRefGoogle Scholar
  14. Miyadera K, Kato K, Aguirre-Hernandez J et al (2009) Phenotypic variation and genotype-­phenotype discordance in canine cone-rod dystrophy with an RPGRIP1 mutation. Mol Vis 15:2287–2305PubMedGoogle Scholar
  15. Mollet G, Salomon R, Gribouval O et al (2002) The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin. Nat Genet 32:300–305PubMedCrossRefGoogle Scholar
  16. Murga-Zamalloa CA, Desai NJ, Hildebrandt F et al (2010) Interaction of ciliary disease protein retinitis pigmentosa GTPase regulator with nephronophthisis-associated proteins in mammalian retinas. Mol Vis 16:1373–1381PubMedGoogle Scholar
  17. Nachury MV, Loktev AV, Zhang Q et al (2007) A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 129:1201–1213PubMedCrossRefGoogle Scholar
  18. Otto EA, Loeys B, Khanna H et al (2005) Nephrocystin-5, a ciliary IQ domain protein, is mutated in senior-loken syndrome and interacts with RPGR and calmodulin. Nat Genet 37:282–288PubMedCrossRefGoogle Scholar
  19. Roepman R, Wolfrum U (2007) Protein networks and complexes in photoreceptor cilia. Subcell Biochem 43:209–235PubMedCrossRefGoogle Scholar
  20. Roepman R, Letteboer SJ, Arts HH et al (2005) Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations. Proc Natl Acad Sci USA 102:18520–18525PubMedCrossRefGoogle Scholar
  21. Roepman R, Bernoud-Hubac N, Schick DE et al (2000) The retinitis pigmentosa GTPase regulator (RPGR) interacts with novel transport-like proteins in the outer segments of rod photoreceptors. Hum Mol Genet 9:2095–2105PubMedCrossRefGoogle Scholar
  22. Ropstad EO, Bjerkas E, Narfstrom K (2007) Clinical findings in early onset cone-rod dystrophy in the standard wire-haired dachshund. Vet Ophthalmol 10:69–75PubMedCrossRefGoogle Scholar
  23. Shu X, Fry AM, Tulloch B et al (2005) RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal bodies and interacts with nucleophosmin. Hum Mol Genet 14:1183–1197PubMedCrossRefGoogle Scholar
  24. Trojan P, Krauss N, Choe HW et al (2008) Centrins in retinal photoreceptor cells: Regulators in the connecting cilium. Prog Retin Eye Res 27:237–259PubMedCrossRefGoogle Scholar
  25. Tsang WY, Bossard C, Khanna H et al (2008) CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease. Dev Cell 15:187–197PubMedCrossRefGoogle Scholar
  26. Tsang WY, Spektor A, Luciano DJ et al (2006) CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol Biol Cell 17:3423–3434PubMedCrossRefGoogle Scholar
  27. Wiik AC, Wade C, Biagi T et al (2008) A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone-rod dystrophy in standard wire-haired dachshund. Genome Res 18:1415–1421PubMedCrossRefGoogle Scholar
  28. Won J, Gifford E, Smith RS et al (2009) RPGRIP1 is essential for normal rod photoreceptor outer segment elaboration and morphogenesis. Hum Mol Genet 18:4329–4339PubMedCrossRefGoogle Scholar
  29. Zhang H, Liu XH, Zhang K et al (2004) Photoreceptor cGMP phosphodiesterase delta subunit (PDEdelta) functions as a prenyl-binding protein. J Biol Chem 279:407–413PubMedCrossRefGoogle Scholar
  30. Zhao Y, Hong DH, Pawlyk B et al (2003) The retinitis pigmentosa GTPase regulator (RPGR)- interacting protein: Subserving RPGR function and participating in disk morphogenesis. Proc Natl Acad Sci USA 100:3965–3970PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Tatyana Kuznetsova
    • 1
    Email author
  • Barbara Zangerl
    • 1
  • Gustavo D. Aguirre
    • 1
  1. 1.Department of Clinical Studies, Section of Ophthalmology, School of Veterinary MedicineUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations