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A Thy1-CFP DBA/2J mouse line with cyan fluorescent protein expression in retinal ganglion cells

Published online by Cambridge University Press:  23 November 2009

IONA D. RAYMOND ,
ANGELA L. POOL ,
ALEJANDRO VILA  and
NICHOLAS C. BRECHA
IONA D. RAYMOND*
Affiliation:
Departments of Neurobiology & Medicine, David Geffen UCLA School of Medicine, Los Angeles, California
ANGELA L. POOL
Affiliation:
Departments of Neurobiology & Medicine, David Geffen UCLA School of Medicine, Los Angeles, California
ALEJANDRO VILA
Affiliation:
Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, Texas
NICHOLAS C. BRECHA
Affiliation:
Departments of Neurobiology & Medicine, David Geffen UCLA School of Medicine, Los Angeles, California CURE, Division of Digestive Diseases, David Geffen UCLA School of Medicine, Los Angeles, California Jules Stein Eye Institute, David Geffen UCLA School of Medicine, Los Angeles, California VAGLAHS, Los Angeles, California
*
*Address correspondence and reprint requests to: Iona D. Raymond, Department of Neurobiology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Box 951763, Los Angeles, CA 90095-1763. E-mail: [email protected]
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Abstract

A DBA/2J (D2) transgenic mouse line with cyan fluorescent protein (CFP) reporter expression in ganglion cells was developed for the analysis of ganglion cells during progressive glaucoma. The Thy1-CFP D2 (CFP-D2) line was created by congenically breeding the D2 line, which develops pigmentary glaucoma, and the Thy1-CFP line, which expresses CFP in ganglion cells. Microsatellite marker analysis of CFP-D2 progeny verified the genetic inclusion of the D2 isa and ipd loci. Specific mutations within these loci lead to dysfunctional melanosomal proteins and glaucomatous phenotype in D2 mice. Polymerase chain reaction analysis confirmed the inclusion of the Thy1-CFP transgene. CFP-fluorescent ganglion cells, 6–20 μm in diameter, were distributed in all retinal regions, CFP processes were throughout the inner plexiform layer, and CFP-fluorescent axons were in the fiber layer and optic nerve head. Immunohistochemistry with antibodies to ganglion cell markers NF-L, NeuN, Brn3a, and SMI32 was used to confirm CFP expression in ganglion cells. Immunohistochemistry with antibodies to amacrine cell markers HPC-1 and ChAT was used to confirm weak CFP expression in cholinergic amacrine cells. CFP-D2 mice developed a glaucomatous phenotype, including iris disease, ganglion cell loss, attrition of the fiber layer, and elevated intraocular pressure. A CFP-D2 transgenic line with CFP-expressing ganglion cells was developed, which has (1) a predominantly D2 genetic background, (2) CFP-expressing ganglion cells, and (3) age-related progressive glaucoma. This line will be of value for experimental studies investigating ganglion cells and their axons in vivo and in vitro during the progressive development of glaucoma.

Keywords

GlaucomaDBA/2JGanglion cellsFluorescent proteinTransgenic mouse
Type
Research Articles
Information
Visual Neuroscience , Volume 26 , Issue 5-6 , November 2009 , pp. 453 - 465
Copyright
Copyright © Cambridge University Press 2009

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References

Anderson, M.G., Smith, R.S., Hawes, N.L., Zabaleta, A., Chang, B., Wiggs, J.L. & John, S.W. (2002). Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. Nature Genetics 30, 81–85.CrossRefGoogle ScholarPubMed
Barnstable, C.J., Hofstein, R. & Akagawa, K. (1985). A marker of early amacrine cell development in rat retina. Brain Research 352, 286–290.Google Scholar
Canola, K., Angenieux, B., Tekaya, M., Quiambao, A., Naash, M.I., Munier, F.L., Schorderet, D.F. & Arsenijevic, Y. (2007). Retinal stem cells transplanted into models of late stages of retinitis pigmentosa preferentially adopt a glial or a retinal ganglion cell fate. Investigative Ophthalmology & Visual Sciences 48, 446–454.Google Scholar
Chang, B., Smith, R.S., Hawes, N.L., Anderson, M.G., Zabaleta, A., Savinova, O., Roderick, T.H., Heckenlively, J.R., Davisson, M.T. & John, S.W. (1999). Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice. Nature Genetics 21, 405–409.Google Scholar
Coombs, J., van der List, D., Wang, G.Y. & Chalupa, L.M. (2006). Morphological properties of mouse retinal ganglion cells. Neuroscience 140, 123–36.Google Scholar
Day, D.A. & Tuite, M.F. (1998). Post-transcriptional gene regulatory mechanisms in eukaryotes: An overview. The Journal of Endocrinology 157, 361–371.CrossRefGoogle ScholarPubMed
Dijk, F., Bergen, A.A. & Kamphuis, W. (2007). GAP-43 expression is upregulated in retinal ganglion cells after ischemia/reperfusion-induced damage. Experimental Eye Research 84, 858–867.Google Scholar
Doi, M., Uji, Y. & Yamamura, H. (1995). Morphological classification of retinal ganglion cells in mice. The Journal of Comparative Neurology 356, 368–386.Google Scholar
Drager, U.C., Edwards, D.L. & Barnstable, C.J. (1984). Antibodies against filamentous components in discrete cell types of the mouse retina. The Journal of Neuroscience 4, 2025–2042.CrossRefGoogle ScholarPubMed
Drager, U.C. & Hofbauer, A. (1984). Antibodies to heavy neurofilament subunit detect a subpopulation of damaged ganglion cells in retina. Nature 309, 624–626.Google Scholar
Dyka, F.M., May, C.A. & Enz, R. (2004). Metabotropic glutamate receptors are differentially regulated under elevated intraocular pressure. Journal of Neurochemistry 90, 190–202.Google Scholar
Feng, G., Mellor, R.H., Bernstein, M., Keller-Peck, C., Nguyen, Q.T., Wallace, M., Nerbonne, J.M., Lichtman, J.W. & Sanes, J.R. (2000). Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51.Google Scholar
Howell, G.R., Libby, R.T., Marchant, J.K., Wilson, L.A., Cosma, I.M., Smith, R.S., Anderson, M.G. & John, S.W. (2007). Absence of glaucoma in DBA/2J mice homozygous for wild-type versions of Gpnmb and Tyrp1. BMC Genetics 8, 45.Google Scholar
Huang, W., Fileta, J., Guo, Y. & Grosskreutz, C.L. (2006). Downregulation of Thy1 in retinal ganglion cells in experimental glaucoma. Current Eye Research 31, 265–271.Google Scholar
Inman, D.M., Sappington, R.M., Horner, P.J. & Calkins, D.J. (2006). Quantitative correlation of optic nerve pathology with ocular pressure and corneal thickness in the DBA/2 mouse model of glaucoma. Investigative Ophthalmology & Visual Sciences 47, 986–996.CrossRefGoogle ScholarPubMed
Inoue, A. & Akagawa, K. (1993). Neuron specific expression of a membrane protein, HPC-1: Tissue distribution, and cellular and subcellular localization of immunoreactivity and mRNA. Brain Research. Molecular Brain Research 19, 121–128.Google Scholar
Inoue, A., Obata, K. & Akagawa, K. (1992). Cloning and sequence analysis of cDNA for a neuronal cell membrane antigen, HPC-1. The Journal of Biological Chemistry 267, 10613–10619.Google Scholar
Jakobs, T.C., Libby, R.T., Ben, Y., John, S.W. & Masland, R.H. (2005). Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice. The Journal of Cell Biology 171, 313–325.Google Scholar
Jeon, C.J., Strettoi, E. & Masland, R.H. (1998). The major cell populations of the mouse retina. The Journal of Neuroscience 18, 8936–8946.CrossRefGoogle ScholarPubMed
John, S.W., Smith, R.S., Savinova, O.V., Hawes, N.L., Chang, B., Turnbull, D., Davisson, M., Roderick, T.H. & Heckenlively, J.R. (1998). Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice. Investigative Ophthalmology & Visual Sciences 39, 951–962.Google Scholar
Kang, T.H., Ryu, Y.H., Kim, I.B., Oh, G.T. & Chun, M.H. (2004). Comparative study of cholinergic cells in retinas of various mouse strains. Cell and Tissue Research 317, 109–115.CrossRefGoogle ScholarPubMed
Kong, J.H., Fish, D.R., Rockhill, R.L. & Masland, R.H. (2005). Diversity of ganglion cells in the mouse retina: Unsupervised morphological classification and its limits. The Journal of Comparative Neurology 489, 293–310.Google Scholar
Kong, W.C. & Cho, E.Y. (1999). Antibodies against neurofilament subunits label retinal ganglion cells but not displaced amacrine cells of hamsters. Life Sciences 64, 1773–1778.Google Scholar
Kuehn, M.H., Fingert, J.H. & Kwon, Y.H. (2005). Retinal ganglion cell death in glaucoma: Mechanisms and neuroprotective strategies. Ophthalmology Clinics of North America 18, 383–395, vi.Google Scholar
Libby, R.T., Anderson, M.G., Pang, I.H., Robinson, Z.H., Savinova, O.V., Cosma, I.M., Snow, A., Wilson, L.A., Smith, R.S., Clark, A.F. & John, S.W. (2005). Inherited glaucoma in DBA/2J mice: Pertinent disease features for studying the neurodegeneration. Visual Neuroscience 22, 637–648.CrossRefGoogle ScholarPubMed
Moon, J.I., Kim, I.B., Gwon, J.S., Park, M.H., Kang, T.H., Lim, E.J., Choi, K.R. & Chun, M.H. (2005). Changes in retinal neuronal populations in the DBA/2J mouse. Cell and Tissue Research 320, 51–59.Google Scholar
Morris, R. (1985). Thy-1 in developing nervous tissue. Developmental Neuroscience 7, 133–160.CrossRefGoogle ScholarPubMed
Morrison, J.C., Johnson, E.C., Cepurna, W. & Jia, L. (2005). Understanding mechanisms of pressure-induced optic nerve damage. Progress in Retinal and Eye Research 24, 217–240.Google Scholar
Nickells, R.W. (1996). Retinal ganglion cell death in glaucoma: The how, the why, and the maybe. Journal of Glaucoma 5, 345–356.Google Scholar
Nickells, R.W. (1999). Apoptosis of retinal ganglion cells in glaucoma: An update of the molecular pathways involved in cell death. Survey of Ophthalmology 43(Suppl. 1), S151–S161.CrossRefGoogle ScholarPubMed
Quigley, H.A. (1995). Ganglion cell death in glaucoma: Pathology recapitulates ontogeny. Australian and New Zealand Journal of Ophthalmology 23, 85–91.CrossRefGoogle ScholarPubMed
Quigley, H.A. (1996). Number of people with glaucoma worldwide. The British Journal of Ophthalmology 80, 389–393.Google Scholar
Quigley, H.A. (1999). Neuronal death in glaucoma. Progress in Retinal and Eye Research 18, 39–57.CrossRefGoogle ScholarPubMed
Quigley, H.A. & Green, W.R. (1979). The histology of human glaucoma cupping and optic nerve damage: Clinicopathologic correlation in 21 eyes. Ophthalmology 86, 1803–1830.Google Scholar
Quina, L.A., Pak, W., Lanier, J., Banwait, P., Gratwick, K., Liu, Y., Velasquez, T., O’Leary, D.D., Goulding, M. & Turner, E.E. (2005). Brn3a-expressing retinal ganglion cells project specifically to thalamocortical and collicular visual pathways. The Journal of Neuroscience 25, 11595–11604.Google Scholar
Raymond, I.D., Vila, A., Huynh, U.C. & Brecha, N.C. (2008). CFP expression in ganglion and amacrine cells in a thy1-CFP transgenic mouse retina. Molecular Vision 14, 1559–1574.Google Scholar
Reitsamer, H.A., Kiel, J.W., Harrison, J.M., Ransom, N.L. & McKinnon, S.J. (2004). Tonopen measurement of intraocular pressure in mice. Experimental Eye Research 78, 799–804.Google Scholar
Ruiz-Ederra, J., Garcia, M., Hicks, D. & Vecino, E. (2004). Comparative study of the three neurofilament subunits within pig and human retinal ganglion cells. Molecular Vision 10, 83–92.Google Scholar
Schlamp, C.L., Johnson, E.C., Li, Y., Morrison, J.C. & Nickells, R.W. (2001). Changes in Thy1 gene expression associated with damaged retinal ganglion cells. Molecular Vision 7, 192–201.Google Scholar
Schlamp, C.L., Li, Y., Dietz, J.A., Janssen, K.T. & Nickells, R.W. (2006). Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric. BMC Neuroscience 7, 66.Google Scholar
Schuettauf, F., Quinto, K., Naskar, R. & Zurakowski, D. (2002). Effects of anti-glaucoma medications on ganglion cell survival: The DBA/2J mouse model. Vision Research 42, 2333–2337.Google Scholar
Schuettauf, F., Rejdak, R., Walski, M., Frontczak-Baniewicz, M., Voelker, M., Blatsios, G., Shinoda, K., Zagorski, Z., Zrenner, E. & Grieb, P. (2004). Retinal neurodegeneration in the DBA/2J mouse-a model for ocular hypertension. Acta Neuropathologica (Berlin) 107, 352–358.Google Scholar
Soto, I., Oglesby, E., Buckingham, B.P., Son, J.L., Roberson, E.D., Steele, M.R., Inman, D.M., Vetter, M.L., Horner, P.J. & Marsh-Armstrong, N. (2008). Retinal ganglion cells downregulate gene expression and lose their axons within the optic nerve head in a mouse glaucoma model. The Journal of Neuroscience 28, 548–561.CrossRefGoogle Scholar
Sun, W., Li, N. & He, S. (2002). Large-scale morphological survey of mouse retinal ganglion cells. The Journal of Comparative Neurology 451, 115–126.Google Scholar
Tian, N. & Copenhagen, D.R. (2003). Visual stimulation is required for refinement of ON and OFF pathways in postnatal retina. Neuron 39, 85–96.Google Scholar
Voigt, T. (1986). Cholinergic amacrine cells in the rat retina. The Journal of Comparative Neurology 248, 19–35.CrossRefGoogle ScholarPubMed
Wang, X., Ng, Y.K. & Tay, S.S. (2005). Factors contributing to neuronal degeneration in retinas of experimental glaucomatous rats. Journal of Neuroscience Research 82, 674–689.CrossRefGoogle ScholarPubMed
Wang, X., Tay, S.S. & Ng, Y.K. (2000). An immunohistochemical study of neuronal and glial cell reactions in retinae of rats with experimental glaucoma. Experimental Brain Research 132, 476–484.Google Scholar
Weber, J.T. (1985). Pretectal complex and accessory optic system of primates. Brain, Behavior and Evolution 26, 117–140.Google Scholar
Williams, R.W., Strom, R.C., Rice, D.S. & Goldowitz, D. (1996). Genetic and environmental control of variation in retinal ganglion cell number in mice. The Journal of Neuroscience 16, 7193–7205.CrossRefGoogle Scholar
Wolf, H.K., Buslei, R., Schmidt-Kastner, R., Schmidt-Kastner, P.K., Pietsch, T., Wiestler, O.D. & Blumcke, I. (1996). NeuN: A useful neuronal marker for diagnostic histopathology. The Journal of Histochemistry and Cytochemistry 44, 1167–1171.Google Scholar
Xiang, M., Zhou, L., Macke, J.P., Yoshioka, T., Hendry, S.H., Eddy, R.L., Shows, T.B. & Nathans, J. (1995). The Brn-3 family of POU-domain factors: Primary structure, binding specificity, and expression in subsets of retinal ganglion cells and somatosensory neurons. The Journal of Neuroscience 15(Pt 1), 4762–4785.CrossRefGoogle ScholarPubMed
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