APOPTOTIC CELL-DEATH OF PHOTORECEPTOR CELLS IN MICE DEFICIENT FOR THEADHESION 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 be ta 2-subunit of the Na,K-ATPase) in mice results in swelling and subse quent degeneration of astrocyte endfeet in the brainstem and in cell d eath of photoreceptor cells in the retina. In the present study, we de monstrate that photoreceptor cells in the mutant develop normally duri ng the first postnatal week. Compared to wild-type mice, a slightly in creased 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 sit u labelling of degenerating cells by terminal dUTP nick end labelling and electron microscopic analysis revealed apoptotic cell death of pho toreceptor cells. Massive degeneration of photoreceptor cells in the m utant at postnatal day 16 correlated with elevated levels of glial fib rillary acidic protein in retinal astrocytes and with expression of th is protein by Muller cells. No evidence was found for degeneration of other retinal cell types or for glial cell death in the optic nerve. O ur observations demonstrate that the pathological death of cells induc ed by disruption of the AMOG/beta 2 gene results from activation of an intrinsic death program, similar to what has been shown to occur duri ng normal development.