Abstract
Abnormalities of the retinal pigment epithelial (RPE) cells are seen in several inherited degenerations such as Best disease (Petrukhin et al., 1998; Marmorstein et al., 2000), Stargardt disease (Weng et al., 1999), Sorsby’s fundus dystrophy (Steinmetz et al., 1992; Jacobson et al., 1995), and childhood-onset severe retinal dystrophy (Gu et al., 1997) and Leber congenital amaurosis due to RPE65 mutations (Marlhens et al., 1997; Morimura et al., 1998; Lotery et al., 2000; Thompson et al., 2000). RCS rats have been studied extensively as a model of photoreceptor (PR)-RPE cell interactions (Mullen and LaVail, 1976; LaVail, 2001) and retinal degeneration (Strauss et al., 1998; LaVail, 2001). Retinal degeneration in RCS results from failure of the RPE to phagocytize shed rod outer segments (OS) (Herron et al., 1969; Bok and Hall, 1971). The unphagocytized OS membranes form membranous whorls at the RPE surface, and the rod OS grow abnormally long (Dowling and Sidman, 1962; LaVail and Battelle, 1975). Eventually, the OS layer degenerates into a debris zone with subsequent PR cell death (Dowling and Sidman, 1962).
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References
Bush, R. A., Hawks, K. W., and Sieving, P. A., 1995, Preservation of inner retinal responses in the aged Royal College of Surgeons rat. Evidence against glutamate excitotoxicity in photoreceptor degenerationInvest Ophthalmol Vis Sci. 36:2054.
Bok, D., and Hall, M. 0., 1971, The role of the pigment epithelium in the etiology of inherited retinal dystrophy in the ratJ Cell Biol. 49:664.
Chen, J., Carey, K., and Godowski, P. J., 1997, Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformationOncogene. 14:2033.
D’Cruz, P. M., Yasumura, D., Weir, J., Matthes, M. T., Abderrahim, H., LaVail, M. M., and Vollrath, D., 2000, Mutation of the receptor tyrosine kinase geneMertkin the retinal dystrophic RCS ratHum Mol Genet . 9:645.
Dowling, J. E., and Sidman, R. L., 1962, Inherited retinal dystrophy in the ratJ Cell Biol. 14:73.
Feng, W., Yasumura, D., Matthes, M. T., LaVail, M. M., and Vollrath, D., 2002, Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cellsJ Biol Chem. 277:17016.
Gal, A., Li, Y., Thompson, D. A., Weir, J., Orth, U., Jacobson, S. G., Apfelstedt-Sylla, E., and Vollrath, D., 2000, Mutations inMERTKthe human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosaNat Genet. 26:270.
Gu, S. M., Thompson, D. A., Srikumari, C. R., Lorenz, B., Finckh, U., Nicoletti, A., Murthy, K. R., Rathmann, M., Kumaramanickavel, G., Denton, M. J., and Gal, A., 1997, Mutations inRPE65cause autosomal recessive childhood-onset severe retinal dystrophyNat Genet. 17:194.
Herron, W. L., Riegel, B. W., Myers, O. E., and Rubin, M. L., 1969, Retinal dystrophy in the rat--a pigment epithelial diseaseInvest Ophthalmol. 8:595.
Jacobson, S. G., Cideciyan, A. V., Regunath, G., Rodriguez, F. J., Vandenburgh, K., Sheffield, V. C., and Stone, E. M., 1995, Night blindness in Sorsby’s fundus dystrophy reversed by vitamin ANat Genet. 11:27.
Kedzierski, W., Lloyd, M., Birch, D. G., Bok, D., and Travis, G. H., 1997, Generation and analysis of transgenic mice expressing P216L-substituted rds/peripherin in rod photoreceptorsInvest Ophthalmol Vis Sci. 38:498.
LaVail, M. M., Sidman, R. L., and O’Neil, D., 1972, Photoreceptor-pigment epithelial cell relationships in rats with inherited retinal degeneration. Radioautographic and electron microscope evidence for a dual source of extra lamellar materialJ Cell Biol. 53:185.
LaVail, M. M., and Battelle, B. A., 1975, Influence of eye pigmentation and light deprivation on inherited retinal dystrophy in the ratExp Eye Res. 21:167.
LaVail, M. M., 1981a, Photoreceptor characteristics in congenic strains of RCS ratsInvest Ophthalmol Vis Sci . 20:671.
LaVail, M. M., 1981b, Analysis of neurological mutants with inherited retinal degeneration. Friedenwald lectureInvest Ophthalmol Vis Sci. 21:638.
LaVail, M. M., 2001, Legacy of the RCS rat: impact of a seminal study on retinal cell biology and retinal degenerative diseases, in:Progress in Brain ResearchH. Kolb, H. Ripps, and S. Wu, ed., Elsevier Science, Paris. pp. 617.
Lotery, A. J., Namperumalsamy, P., Jacobson, S. G., Weleber, R. G., Fishman, G. A., Musarella, M. A., Hoyt, C. S., Heon, E., Levin, A., Jan, J., Lam, B., Carr, R. E., Franklin, A., Radha, S., Andorf, J. L., Sheffield, V. C., and Stone, E. M., 2000, Mutation analysis of 3 genes in patients with Leber congenital amaurosisArch Ophthalmol. 118:538.
Machida, S., Kondo, M., Jamison, J. A., Khan, N. W., Kononen, L. T., Sugawara, T., Bush, R. A., and Sieving, P. A., 2000, P23H rhodopsin transgenic rat: correlation of retinal function with histopathologyInvest Ophthalmol Vis Sci. 41:3200.
Marlhens, F., Bareil, C., Griffoin, J. M., Zrenner, E., Amalric, P., Eliaou, C., Liu, S. Y., Harris, E., Redmond, T. M., Arnaud, B., Claustres, M., and Hamel, C. P., 1997, Mutations inRPE65cause Leber’s congenital amaurosisNat Genet. 17:139.
Marmorstein, A. D., Marmorstein, L. Y., Rayborn, M., Wang, X., Hollyfield, J. G., and Petrukhin, K., 2000, Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epitheliumProc Nall Acad Sci USA. 97:12758.
Morimura, H., Fishman, G. A., Grover, S. A., Fulton, A. B., Berson, E. L., and Dryja, T. P., 1998, Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosisProc Nall Acad Sci USA. 95:3088.
Mullen, R. J., and LaVail, M. M., 1976, Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimerasScience. 192:799.
Nagata, K., Ohashi, K., Nakano, T., Arita, H., Zong, C., Hanafusa, H., and Mizuno, K., 1996, Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinasesJBiol Chem. 271:30022.
Nishikawa, S., Cao, W., Yasumura, D., Matthes, M. T., Lau-Villacorta, C., Steinberg, R. H., and LaVail, M. M., 1997, Comparing the ERG to retinal morphology in transgenic rats with inherited degenerations caused by mutant opsin genes [ARVO Abstract]Invest Ophthalmol Vis Sci.38:S33. Abstract nr 1415.
Petrukhin, K., Koisti, M. J., Bakall, B., Li, W., Xie, G., Marknell, T., Sandgren, O., Forsman, K., Holmgren, G., Andreasson, S., Vujic, M., Bergen, A. A., McGarty-Dugan, V., Figueroa, D., Austin, C. P., Metzker, M. L., Caskey, C. T., and Wadelius, C., 1998, Identification of the gene responsible for Best macular dystrophyNat Genet. 19:241.
Saszik, S. M., Robson, J. G., and Frishman, L. J., 2002, The scotopic threshold response of the dark-adapted electroretinogram of the mouseJPhysiol. 543:899.
Scott, R. S., McMahon, E. J., Pop, S. M., Reap, E. A., Caricchio, R., Cohen, P. L., Earp, H. S., and Matsushima, G. K., 2001, Phagocytosis and clearance of apoptotic cells is mediated by MERNature. 411:207.
Sieving, P. A., Frishman, L. J., and Steinberg, R. H., 1986, Scotopic threshold response of proximal retina in catJ Neurophysiol. 56:1049.
Steinmetz, R. L., Polkinghorne, P. C., Fitzke, F. W., Kemp, C. M., and Bird, A. C., 1992, Abnormal dark adaptation and rhodopsin kinetics in Sorsby’s fondus dystrophyInvest Ophthalmol Vis Sci. 33:1633.
Strauss, O., Stumpff, F., Mergler, S., Wienrich, M., and Wiederholt, M., 1998, The Royal College of Surgeons rat: an animal model for inherited retinal degeneration with a still unknown genetic defectActa Anat. 162:101.
Sugawara, T., Sieving, P. A., and Bush, R. A., 2000, Quantitative relationship of the scotopic and photopic ERG to photoreceptor cell loss in light damaged ratsExp Eye Res . 70:693.
Thompson, D. A., Gyurus, P., Fleischer, L. L., Bingham, E. L., McHenry, C. L., Apfelstedt-Sylla, E., Zrenner, E., Lorenz, B., Richards, J. E., Jacobson, S. G., Sieving, P. A., and Gal, A., 2000, Genetics and phenotypes ofRPE65mutations in inherited retinal degenerationInvest Ophthalmol Vis Sci. 41:4293.
Toda, K., Bush, R. A., Humphries, P., and Sieving, P. A., 1999, The electroretinogram of the rhodopsin knockout mouseVis Neurosci. 16:391.
Varnum, B. C., Young, C., Elliott, G., Garcia, A., Bartley, T. D., Fridell, Y. W., Hunt, R. W., Trail, G., Clogston, C., Toso, R. J., and et al., 1995, Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6Nature. 373:623.
Vollrath, D., Feng, W., Duncan, J. L., Yasumura, D., D’Cruz, P. M., Chappelow, A., Matthes, M. T., Kay, M. A., and LaVail, M. M., 2001, Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer ofMertk Proc Natl Acad Sci USA. 98:12584.
Weng, J., Mata, N. L., Azarian, S. M., Tzekov, R. T., Birch, D. G., and Travis, G. H., 1999, Insights into the function of Rim protein in photoreceptors and etiology of Stargardt’s disease from the phenotype inabcrknockout miceCell. 98:13.
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Duncan, J.L. et al. (2003). Inherited Retinal Dystrophy in Mer Knockout Mice. In: LaVail, M.M., Hollyfield, J.G., Anderson, R.E. (eds) Retinal Degenerations. Advances in Experimental Medicine and Biology, vol 533. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0067-4_21
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DOI: https://doi.org/10.1007/978-1-4615-0067-4_21
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