Targeted inactivation of synaptic HRG4 (UNC119) causes dysfunction in the distal photoreceptor and slow retinal degeneration, revealing a new function

Experimental Eye Research

Volumn 84, Issue 3, 2007, Pages 473-485

  Ishiba, Yasutsugu ^a   Higashide, Tomomi ^a   Mori, Naoki ^a   Kobayashi, Akira ^a   Kubota, Shinya ^a   McLaren, Margaret J ^b   Satoh, Hiromasa ^c   Wong, Fulton ^c   Inana, George ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b Gray Matter Research   (United States)

^c DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

inner segments; knock out model; outer segments; photoreceptor; retinal degeneration; synapse; transgenic model

Indexed keywords

EYE PROTEIN; HUMAN RETINAL GENE 4; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CONTROLLED STUDY; ELECTRORETINOGRAM; EYE FUNDUS; FEMALE; GENE FUNCTION; GENE INACTIVATION; GENE LOCATION; GENOMICS; IMMUNOFLUORESCENCE; KNOCKOUT MOUSE; MOLECULAR CLONING; MOUSE; NICK END LABELING; NONHUMAN; OPHTHALMOSCOPY; PHENOTYPE; PHOTORECEPTOR; PRIORITY JOURNAL; PROTEIN FUNCTION; RETINA DEGENERATION; SOUTHERN BLOTTING; SYNAPSE; WESTERN BLOTTING;

ANIMALS; APOPTOSIS; BLOTTING, WESTERN; CLONING, MOLECULAR; ELECTRORETINOGRAPHY; FLUORESCENT ANTIBODY TECHNIQUE; FUNDUS OCULI; GENE TARGETING; HUMANS; IN SITU NICK-END LABELING; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; MICROTUBULE PROTEINS; MODELS, ANIMAL; MUTATION; PHOTORECEPTORS, VERTEBRATE; RETINA; RETINAL DEGENERATION; SYNAPSES;

EID: 33846827273     PISSN: 00144835     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.exer.2006.10.016     Document Type: Article

References (38)

1. Acland G.M., Aguirre G.D., Ray J., Zhang Q., Aleman T.S., Cideciyan A.V., Pearce-Kelling S.E., Anand V., Zeng Y., Maguire A.M., Jacobson S.G., Hauswirth W.W., and Bennett J. Gene therapy restores vision in a canine model of childhood blindness. Nat. Genet. 28 (2001) 92-95
2. Bowes C., Li T., Danciger M., Baxter L.C., Applebury M.L., and Farber D.B. Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Nature 347 (1990) 677-680
3. Burns M.E., Mendez A., Chen C.K., Almuete A., Quillinan N., Simon M.I., Baylor D.A., and Chen J. Deactivation of phosphorylated and nonphosphorylated rhodopsin by arrestin splice variants. J. Neurosci. 26 (2006) 1036-1044
4. Calvert P.D., Krasnoperova N.V., Lyubarsky A.L., Isayama T., Nicolo M., Kosaras B., Wong G., Gannon K.S., Margolskee R.F., Sidman R.L., Pugh Jr. E.N., Makino C.L., and Lem J. Phototransduction in transgenic mice after targeted deletion of the rod transducin alpha-subunit. Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 13913-13918
5. Calvert P.D., Govardovskii V.I., Krasnoperova N., Anderson R.E., Lem J., and Makino C.L. Membrane protein diffusion sets the speed of rod phototransduction. Nature 411 (2001) 90-94
6. Dryja T.P., McGee T.L., Reichel E., Hahn L.B., Cowley G.S., Yandell D.W., Sandberg M.A., and Berson E.L. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343 (1990) 364-366
7. Dryja T.P., Hahn L.B., Reboul T., and Arnaud B. Missense mutation in the gene encoding the alpha subunit of rod transducin in the Nougaret form of congenital stationary night blindness. Nat. Genet. 13 (1996) 358-360
8. Fan J., Rohrer B., Moiseyev G., Ma J.X., and Crouch R.K. Isorhodopsin rather than rhodopsin mediates rod function in RPE65 knock-out mice. Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 13662-13667 Epub 2003 Oct 24
9. Frederick J.M., Krasnoperova N.V., Hoffmann K., Church-Kopish J., Ruther K., Howes K., Lem J., and Baehr W. Mutant rhodopsin transgene expression on a null background. Investig. Ophthalmol. Vis. Sci. 42 (2001) 826-833
10. Ghetti B., Horoupian D.S., and Wisniewski H.M. Transsynaptic response of the lateral geniculate nucleus and the pattern of degeneration of the nerve terminals in the rhesus monkey after eye enucleation. Brain Res. 45 (1972) 31-48
11. Higashide T., Murakami A., McLaren M.J., and Inana G. Cloning of the cDNA for a novel photoreceptor protein. J. Biol. Chem. 271 (1996) 1797-1804
12. Higashide T., McLaren M.J., and Inana G. Localization of HRG4, a photoreceptor protein homologous to Unc-119, in ribbon synapse. Investig. Ophthalmol. Vis. Sci. 39 (1998) 690-698
13. Higashide T., and Inana G. Characterization of the gene for HRG4 (UNC119), a novel photoreceptor synaptic protein homologous to unc119. Genomics 57 (1999) 446-450
14. Humphries M.M., Rancourt D., Farrar G.J., Kenna P., Hazel M., Bush R.A., Sieving P.A., Sheils D.M., McNally N., Creighton P., Erven A., Boros A., Gulya K., Capecchi M.R., and Humphries P. Retinopathy induced in mice by targeted disruption of the rhodopsin gene. Nat. Genet. 15 (1997) 216-219
15. Jones B.W., Watt C.B., Frederick J.M., Baehr W., Chen C.K., Levine E.M., Milam A.H., Lavail M.M., and Marc R.E. Retinal remodeling triggered by photoreceptor degenerations. J. Comp. Neurol. 464 (2003) 1-16
16. Kedzierski W., Nusinowitz S., Birch D., Clarke G., McInnes R.R., Bok D., and Travis G.H. Deficiency of rds/peripherin causes photoreceptor death in mouse models of digenic and dominant retinitis pigmentosa. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 7718-7723
17. Kobayashi A., Higashide T., Hamasaki D., Kubota S., Sakuma H., An W., Fujimaki T., McLaren M.J., Weleber R.G., and Inana G. HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model. Investig. Ophthalmol. Vis. Sci. 41 (2000) 3268-3277
18. Kobayashi A., Kubota S., Mori N., McLaren M.J., and Inana G. Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain. FEBS Lett. 534 (2003) 26-32
19. Kubota S., Kobayashi A., Mori N., Higashide T., McLaren M.J., and Inana G. Changes in retinal synaptic proteins in the transgenic model expressing a mutant HRG4 (UNC119). Investig. Ophthalmol. Vis. Sci. 43 (2002) 308-313
20. Lee E.S., Burnside B., and Flannery J.G. Characterization of peripherin/rds and rom-1 transport in rod photoreceptors of transgenic and knockout animals. Investig. Ophthalmol. Vis. Sci. 47 (2006) 2150-2160
21. Lem J., Krasnoperova N.V., Calvert P.D., Kosaras B., Cameron D.A., Nicolo M., Makino C.L., and Sidman R.L. Morphological, physiological, and biochemical changes in rhodopsin knockout mice. Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 736-741
22. Maduro M., and Pilgrim D. Identification and cloning of unc-119, a gene expressed in the Caenorhabditis elegans nervous system. Genetics 141 (1995) 977-988
23. Maeda A., Maeda T., Imanishi Y., Kuksa V., Alekseev A., Bronson J.D., Zhang H., Zhu L., Sun W., Saperstein D.A., Rieke F., Baehr W., and Palczewski K. Role of photoreceptor-specific retinol dehydrogenase in the retinoid cycle in vivo. J. Biol. Chem. 280 (2005) 18822-18832 Epub 2005 Mar 8
24. Manning A.G., Crawford B.D., Waskiewicz A.J., and Pilgrim D.B. unc-119 homolog required for normal development of the zebrafish nervous system. Genesis 40 (2004) 223-230
25. Michaelides M., Aligianis I.A., Holder G.E., Simunovic M., Mollon J.D., Maher E.R., Hunt D.M., and Moore A.T. Cone dystrophy phenotype associated with a frameshift mutation M280fsX291 in the alpha-subunit of cone specific transducin (GNAT2). Br. J. Ophthalmol. 87 (2003) 1317-1320 Erratum in: Br. J. Ophthalmol. 2004. 88, 314
26. Mori N., Ishiba Y., Kubota S., Kobayashi A., Higashide T., McLaren M.J., and Inana G. Truncation mutation in HRG4 (UNC119) leads to mitochondrial ANT-1-mediated photoreceptor synaptic and retinal degeneration by apoptosis. Investig. Ophthalmol. Vis. Sci. 47 (2006) 1281-1292
27. Naash M.I., Wu T.H., Chakraborty D., Fliesler S.J., Ding X.Q., Nour M., Peachey N.S., Lem J., Qtaishat N., Al-Ubaidi M.R., and Ripps H. Retinal abnormalities associated with the G90D mutation in opsin. J. Comp. Neurol. 478 (2004) 149-163
28. Palczewski K., Van Hooser J.P., Garwin G.G., Chen J., Liou G.I., and Saari J.C. Kinetics of visual pigment regeneration in excised mouse eyes and in mice with a targeted disruption of the gene encoding interphotoreceptor retinoid-binding protein or arrestin. Biochemistry 38 (1999) 12012-12019
29. Pittler S.J., and Baehr W. Identification of a nonsense mutation in the rod photoreceptor cGMP-phosphodiesterase beta-subunit gene of the rd mouse. Proc. Natl. Acad. Sci. U.S.A. 88 (1991) 8322-8326
30. Ripps H., Peachey N.S., Xu X., Nozell S.E., Smith S.B., and Liou G.I. The rhodopsin cycle is preserved in IRBP "knockout" mice despite abnormalities in retinal structure and function. Vis. Neurosci. 17 (2000) 97-105
31. Rohrer B. Gene dosage effect of the TrkB receptor on rod physiology and biochemistry in juvenile mouse retina. Mol. Vis. 7 (2001) 288-296
32. Sambrook J., Fritsch E.F., and Maniatis T. Molecular Cloning: A Laboratory Manual. second ed. (1989), Cold Spring Harbor, New York
33. Sokolov M., Strissel K.J., Leskov I.B., Michaud N.A., Govardovskii V.I., and Arshavsky V.Y. Phosducin facilitates light-driven transducin translocation in rod photoreceptors. Evidence from the phosducin knockout mouse. J. Biol. Chem. 279 (2004) 19149-19156 Epub 2004 Feb 18
34. Südhof T.C. The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature 375 (1995) 645-653
35. Tsang S.H., Burns M.E., Calvert P.D., Gouras P., Baylor D.A., Goff S.P., and Arshavsky V.Y. Role for the target enzyme in deactivation of photoreceptor G protein in vivo. Science 282 (1998) 117-121
36. Tybulewicz V.L., Crawford C.E., Jackson P.K., Bronson R.T., and Mulligan R.C. Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell 65 (1991) 1153-1163
37. Wachtmeister L. Oscillatory potentials in the retina: what do they reveal?. Prog. Ret. Eye Res. 17 (1998) 485-521
38. Wistow G., Bernstein S.L., Wyatt K., Ray S., Behal A., Touchman J.W., Bouffard G., Smith D., and Peterson K. Expressed sequence tag analysis of human retina for the NEIBank Project: retbindin, an abundant, novel retinal cDNA and alternative splicing of other retina-preferred gene transcripts. Mol. Vis. 8 (2002) 196-204