Age-dependent disruption of basal lamina and extracellular matrix formation in L-proline analog treated otic explants

L-azetidine-2-carboxylic acid, LACA, a naturally occurring vegetable imino acid, can be incorporated into mammal proteins instead of proline. This incorporation has an especially inhibitive effect on collagen secretion. Exposure of embryonic mouse inner ear explants to LACA causes dysmorphogenesis and retarded differentiation, reduces the number of collagen fibrils in the perilymphatic spaces and capsules, and gives rise to a dose-dependent derangement of the basal lamina. In control specimens, both in vivo and in vitro, the inner ear epithelia had a dense contiguous basal lamina overlying a well-developed network of collagen fibrils. When the inner ears were exposed to LACA at a concentration of 150 micrograms per ml of medium, there was a loss of the collagen network and gaps appeared in the basal lamina. At exposure to 300 micrograms LACA/ml, scarcely any collagen fibrils were present and the basal lamina was disrupted in many areas, especially beneath the sensory epithelia.