FINE-STRUCTURE OF EXTRACELLULAR-MATRIX AND BASAL LAMINAE IN 2 TYPES OF ABNORMAL COLLAGEN PRODUCTION - L-PROLINE ANALOG-TREATED OTOCYST CULTURES AND DISPROPORTIONATE MICROMELIA (DMM DMM) MUTANTS/

L-Azetidine-2-carboxylic acid (LACA), a naturally occurring vegetable imino acid, can be incorporated into mammalian proteins in place of pr oline, thereby eliciting an inhibitory effect on collagen secretion. E xposure of explants of the embryonic mouse inner ear to LACA reduces t he number of collagen fibrils in the otic capsule, gives rise to a dos e-dependent derangement of the basal lamina, and ultimately results in dysmorphogenesis and retarded differentiation of the inner ear. Dispr oportionate micromelia (Dmm) is an incomplete dominant form of dwarfis m characterized by a reduced quantity of type II collagen in the carti laginous extracellular matrix (ECM). Abnormal morphogenesis in homozyg otic Dmm mice resembles the abnormal morphogenesis observed in LACA-ex posed otic explants, resulting in malformed inner ears with a bulky ca rtilaginous capsule and a lack or reduction of defined perilymphatic s paces (Van De Water and Galinovic-Schwartz, 1987). In this study, we e xamined by ultrastructural analysis LACA-exposed otic explants and inn er 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 reduction in colla gen fibrils and irregular cytodifferentiation of chondrocytes in the E CM of LACA-exposed and Dmm/Dmm inner ears as well as in the basal lami nae of LACA-exposed specimens. In addition, we provide evidence of dys morphogenesis of the otic capsule and perilymphatic spaces in LACA-exp osed explants. Moreover, while previous studies demonstrated the anoma lous development of sensory structures in otocyst explants following L ACA exposure, in this study we provide evidence of the normal morphoge nesis of otic epithelial-derived sensory structures in homozygotic Dmm /Dmm mouse embryos.