Abstract
L-Azetidine-2-carboxylic acid (LACA), a naturally occurring vegetable imino acid, can be incorporated into mammalian proteins in place of proline, thereby eliciting an inhibitory effect on collagen secretion. Exposure of explants of the embryonic mouse inner ear to LACA reduces the number of collagen fibrils in the otic capsule, gives rise to a dose-dependent derangement of the basal lamina, and ultimately results in dysmorphogenesis and retarded differentiation of the inner ear. Disproportionate micromelia (Dmm) is an incomplete dominant form of dwarfism characterized by a reduced quantity of type II collagen in the cartilaginous extracellular matrix (ECM). Abnormal morphogenesis in homozygotic Dmm mice resembles the abnormal morphogenesis observed in LACA-exposed otic explants, resulting in malformed inner ears with a bulky cartilaginous capsule and a lack or reduction of defined perilymphatic spaces (Van De Water and Galinovic-Schwartz, 1987). In this study, we examined by ultrastructural analysis LACA-exposed otic explants and inner ears of Dmm/Dmm mouse embryos for abnormalities in the collagenous constituents of the basal laminae and capsular ECM. We demonstrate, in comparison to normal embryonic mouse inner ears, a reduc...Continue Reading
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Oct 31, 2009·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Lilach M Friedman, Karen B Avraham
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