Apoptotic cell death of photoreceptor cells in mice deficient for the adhesion molecule on glia (AMOG, the beta 2- subunit of the Na, K-ATPase).
Disruption of the gene for the adhesion molecule on glia (AMOG, the beta 2-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/beta 2-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 Muller 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/beta 2 gene results from activation of an intrinsic death program, similar to what has been shown to occur during normal development.
Molthagen
M
M
Department of Neurobiology, Swiss Federal Institute of Technology, Hönggerberg, Zürich, Switzerland.
Schachner
M
M
Bartsch
U
U
D000251:Adenosine Triphosphatases; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D027682:Cation Transport Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009900:Optic Nerve / Q000166:cytology / Q000502:physiology; D010786:Photoreceptor Cells / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D011995:Recombination, Genetic; D012016:Reference Values; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D000254:Sodium-Potassium-Exchanging ATPase / Q000172:deficiency* / Q000235:genetics
C504191:Atp1b2 protein, mouse; D015415:Biomarkers; D027682:Cation Transport Proteins; D015816:Cell Adhesion Molecules, Neuronal; D005904:Glial Fibrillary Acidic Protein; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase