Summary
Disruption of the gene for the adhesion molecule on glia (AMOG, the β2-subunit of the Na, K-ATPase) in mice results in swelling and subsequent degeneration of astrocyte endfeet in the brainstem and in cell death of photoreceptor cells in the retina. In the present study, we demonstrate that photoreceptor cells in the mutant develop normally during the first postnatal week. Compared to wild-type mice, a slightly increased density of degenerating photoreceptor cells became apparent in 9-day-old mutants and numerous degenerating photoreceptor cells were present in the retina of 16-day-old AMOG/β2-deficient mice.In situ labelling of degenerating cells by terminal dUTP nick end labelling and electron microscopic analysis revealed apoptotic cell death of photoreceptor cells. Massive degeneration of photoreceptor cells in the mutant at postnatal day 16 correlated with elevated levels of glial fibrillary acidic protein in retinal astrocytes and with expression of this protein by Müller cells. No evidence was found for degeneration of other retinal cell types or for glial cell death in the optic nerve. Our observations demonstrate that the pathological death of cells induced by disruption of the AMOG/β2 gene results from activation of an intrinsic death program, similar to what has been shown to occur during normal development.
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References
Antonicek, H. &Schachner, M. (1988) The adhesion molecule on glia (AMOG) incorporated into lipid vesicles binds to subpopulations of neurons.Journal of Neuroscience 8, 2961–6.
Antonicek, H., Persohn, E. &Schachner, M. (1987) Biochemical and functional characterization of a novel neuron-glia adhesion molecula that is involved in neuronal migration.Journal of Cell Biology 104, 1587–95.
Barres, B. A., Hart, I. K., Coles, H. S. R., Burne, J. F., Voyvodic, J. T., Richardson, W. D. &Raff, M. C. (1992) Cell death and control of cell survival in the oligodendrocyte lineage.Cell 70, 31–46.
Bartsch, S., Bartsch, U., Dörries, U., Faissner, A., Weller, A., Ekblom, P. &Schachner, M. (1992) Expression of tenascin in the developing and adult cerebellar cortex.Journal of Neuroscience 12, 736–49.
Bartsch, U., Kirchhoff, F. &Schachner, M. (1989) Immunohistological localization of the adhesion molecules L1, N-CAM, and MAG in the developing and adult optic nerve of mice.Journal of Comparative Neurology 284, 451–62.
Bartsch, U., Faissner, A., Trotter, J., Dörries, U., Bartsch, S., Mohajeri, H. &Schachner, M. (1994) Tenascin demarcates the boundary between the myelinated and nonmyelinated part of retinal ganglion cell axons in the developing and adult mouse.Journal of Neuroscience 14, 4756–68.
Carter-Dawson, L. D. &Lavail, M. M. (1979) Rods and cones in the mouse ratina. II. Autoradiographic analysis of cell generation using triated thymidine.Journal of Comparative Neurology 188, 263–72.
Chang, G.-Q., Hao, Y. &Wong, F. (1993) Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice.Neuron 11, 595–605.
Dörries, U., Bartsch, U., Nolte, C., Roth, J. &Schachner, M. (1993) Adaptation of a non-radioactivein situ hybridization method to electron microscopy: detection of tenascin mRNAs in mouse cerebellum with digoxigenin-labelled probes and gold-labelled antibodies.Histochemistry 99, 251–62.
Eisenfeld, A. J., Bunt-Milam, A. H. &Sarthy, P. V. (1984) Müller cell expression of glial fibrillary acidic protein after genetic and experimental photoreceptor degeneration in the rat retina.Investigative Ophthalmology and Visual Science 25, 1321–8.
Ellis, R. E., Yuan, J. &Horvitz, H. R. (1991) Mechanisms and functions of cell death.Annual Review of Cell Biology 7, 663–98.
Garcia, I., Martinou, I., Tsujimoto, Y. &Martinou, J.-C. (1992) Prevention of programmed cell death of sympathetic neurons by thebcl-2 proto-oncogene.Science 258, 302–4.
Gavrieli, Y., Sherman, Y. &Ben-Sasson, S. A. (1992) Identification of programmed cell deathin situ via specific labeling of nuclear DNA fragmentation.Journal of Cell Biology 119, 493–501.
Geering, K. (1991) The functional role of the β-subunit in the maturation and intracellular transport of Na, K-ATPase.FEBS Letters 285, 189–93.
Geering, K., Theulaz, I., Verrey, F., Häuptle, M. T. &Rossier, B. C. (1989) A role for the β-subunit in the expression of functional Na+−K+-ATPase inXenopus oocytes.American Journal of Physiology 257, 851–8.
Gloor, S., Antonicek, H., Sweadner, K. J., Pagliusi, S., Frank, R., Moos, M. &Schachner, M. (1990) The adhesion molecule on glia (AMOG) is a homologue of the β-subunit of the Na, K-ATPase.Journal of Cell Biology 110, 165–74.
Isenmann, S., Molthagen, M., Brandner, S., Bartsch, U. Kühne, G., Magyar, J. P., Sure, U., Schachner, M. & Aguzzi, A. The AMOG/β2-subunit of the Na, K-ATPase is not necessary for long-term servival of telencephalic grafts.Glia (1995), 377–88.
Krueger, B. K., Burne, J. F. &Raff, M. C. (1995) Evidence for large-scale astrocyte death in the developing cerebellum.Journal of Neuroscience 15, 3366–74.
Lolley, R. N., Rong, H. &Craft, C. M. (1994) Linkage of photoreceptor degeneration by apoptosis with inherited defect in phototransduction.Investigative Ophthalmology and Visual Science 35, 358–62.
Magyar, J. P., Bartsch, U., Wang, Z.-Q., Howells, N., Aguzzi, A., Wagner, E. F. &Schachner, M. (1994) Degeneration of neural cells in the central nervous system of mice deficient in the gene for the adhesion molecule on glia, the β2-subunit of murine Na, K-ATPase.Journal of Cell Biology 127, 835–45.
Martinou, J.-C., Dubois-Dauphin, M., Stalpe, J. K., Rodriguez, I., Frankowski, H., Missotten, M., Albertini, P., Talabot, D., Catsicas, S., Pietra, C. &Huarte, J. (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia.Neuron 13, 1017–30.
Müller-Husmann, G., Gloor, S. &Schachner, M. (1993) Functional characterization of β-isoforms of murine Na, K-ATPase.Journal of Biological Chemistry 268, 26260–7.
Oppenheim, R. W. (1985) Naturally occurring cell death during neural development.Trends in Neurosciences 8, 487–93.
Oppenheim, R. W. (1991) Cell death during development of the nervous system.Annual Review of Neuroscience 14, 453–501.
Pagliusi, S. R., Schachner, M., Seeburg, P. H. &Shivers, B. D. (1990) The adhesion molecule on glia (AMOG) is widely expressed by astrocytes in developing and adult mouse brain.European Journal of Neuroscience 2, 471–80.
Papermaster, D. S. &Windle, J. (1995) Death at an early age. Apoptosis in inherited retinal degenerations.Investigative Ophthalmology and Visual Science 36 977–83.
Portera-Cailliau, C., Sung, C.-H., Nathans, J. &Adler, R. (1994) Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa.Proceedings of the National Academy of Sciences (USA) 91, 974–8.
Rabacchi, S. A., Bonfanti, L., Liu, X.-H. &Maffel, L. (1994) Apoptotic cell death induced by optic nerve lesion in the neonatal rat.Journal of Neuroscience 14, 5292–301.
Raff, M. C. (1992) Social controls on cell survival and cell death.Nature 356, 397–400.
Raff, M. C., Barres, B. A., Burne, J. F., Coles, H. S., Ishizaki, Y. &Jacobson, M. D. (1993) Programmed cell death and the control of cell survival: lessons from the nervous system.Science 262, 695–700.
Robinson, S. R. (1988) Cell death in the inner and outer nuclear layers of the developing cat retina.Journal of Comparative Neurology 267, 507–15.
Schmalzing, G., Kröner, S., Schachner, M. &Gloor, S. (1992) The adhesion molecule on glia (AMOG/β2) and α1 subunits assemble to functional sodium pumps inXenopus oocytes.Journal of Biological Chemistry 267, 20212–16.
Schneider, B. G., Shyjan, A. W. &Levenson, R. (1991) Co-localization and polarized distribution of Na, K-ATPase α3 and β2 subunits in photoreceptor cells.Journal of Histochemistry and Cytochemistry 39, 507–17.
Semple-Rowland, S. L. (1991) Expression of glial fibrillary acidic protein by Müller cells inrd chick retina.Journal of Comparative Neurology 305, 582–90.
Sidman, R. L. (1961) Histogenesis of mouse retina studied with thymidine-H3. InThe Structure of the Eye (edited bySmelser, G.) pp. 487–506. New York: Academic Press.
Spira, A., Hudy, S. &Hannah, R. (1984) Ectopic photoreceptor cells and cell death in the developing rat retina.Anatomy and Embryology 169, 293–301.
Sweadner, K. J. (1989) Isozymes of the Na+/K+-ATPase.Biochimica et Biophysica Acta 988, 185–220.
Thompson, C. B. (1995) Apoptosis in the pathogenesis and treatment of disease.Science 267, 1456–62.
Tso, M. O. M., Zhang, C., Abler, A. S., Chang, C.-J., Wong, F., Chang, G.-Q. &Lam, T. T. (1994) Apoptosis leads to photoreceptor degeneration in inherited retinal dystrophy of RCS rats.Investigative Ophthalmology and Visual Science 35, 2693–9.
Wood, K. A., Dipasquale, B. &Youle, R. J. (1993)In situ labeling of granule cells for apoptosis-associated DNA fragmentation reveals different mechanisms of cell loss in developing cerebellum.Neuron 11, 621–32.
Young, R. W. (1984) Cell death during differentiation of the retina in the mouse.Journal of Comparative Neurology 229, 362–73.
Young, R. W. (1985) Cell differentiation in the retina of the mouse.Anatomical Record 212, 199–205.
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Molthagen, M., Schachner, M. & Bartsch, U. Apoptotic cell death of photoreceptor cells in mice deficient for the adhesion molecule on glia (AMOG, the β2-subunit of the Na,K-ATPase). J Neurocytol 25, 243–255 (1996). https://doi.org/10.1007/BF02284800
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DOI: https://doi.org/10.1007/BF02284800