Caspase-3-deficiency induces hyperplasia of supporting cells and degeneration of sensory cells resulting in the hearing loss

Caspase-3 is one of the cystein proteases that play essential roles in prog rammed cell death. As such, brain development is profoundly affected by cas pase-3-deficiency, resulting in hyperplasia and abnormal cell organization (Kuida et al., Nature 1996;384:368-372). In the present study, we used casp ase-3 (-/-) mice to show that caspase-3 deficiency results in severe hearin g loss, hyperplasia of supporting cells and degeneration of sensory hair ce lls. The greater epithelial ridge, a remnant of the primordial organ of Cor ti, persists throughout all of the turns of cochlea in 2-week-old caspase-3 (-/-) mice, which indicates that the morphology of the cochlea is immature . The number of border cells, that develop from the greater epithelial ridg e and are one of the supporting cells of the inner hair cell, increase sign ificantly in both 2- and 5-week-old caspase-3 (-/-) mice. On the other hand , abnormal fused stereocilia can be seen in both 2- and 5-week-old caspase- 3 (-/-) mice, and disarrangement and loss of sensory hair cells are observe d in 5-week-old caspase-3 (-/-) mice. Taken together, both hyperplasia and degeneration occur simultaneously in the inner ear of the caspase-3 (-/-) m ice, suggesting that caspase-3-dependent apoptosis is necessary for the dev elopment and formation of a properly functioning auditory system in mammals . (C) 2001 Elsevier Science B.V. All rights reserved.