Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A massive loss of inner hair cells typifies the cochleae of Bronx waltzer mutant mice. We have characterized the surviving inner hair cells and their modified innervation by immunocytochemistry using antibodies against neuron-specific enolase, with additional stains for neural cell adhesion molecule and neurofilaments, and by electron microscopy. The surviving inner hair cells vary in size, neuron-specific enolase content and innervation. All neuron-specific enolase-positive cells are innervated by neuron-specific enolase-positive endings. There is apparent correspondence between the neuron-specific enolase immunoreactivity of sensory cells and their innervation. Well-stained cells are richly innervated (and large) while lightly stained cells received fewer nerve endings. Neuron-specific enolase-negative inner hair cells innervated either by neuron-specific enolase-positive or -negative nerve endings are very rare. Ultrastructurally, the surviving inner hair cells vary from those of a normal morphological appearance to underdeveloped or vacuolated. Most of the apparently normal inner hair cells are associated with few nerve endings; instead nerve growth cones are abundant in the adjacent inner spiral sulcus epithelium. Cells forming ribbon synapses with afferent endings are rare. The contingent of efferent endings in the inner spiral bundle depends on the presence of afferent endings. The absence of inner hair cells and the uneven distribution of nerve endings on the surviving cells results in the disruption of normal innervation patterns, especially in the thinning out or discontinuation of the inner spiral bundle and an uneven distribution of tunnel fibres. We infer that the sprouting of nerve endings and their convergence on a selected population of the surviving inner hair cells represents a compensatory regenerative phenomenon in response to the loss and the genetic defect of the remaining inner hair cells.
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PMID:Patterns of hair cell survival and innervation in the cochlea of the bronx waltzer mouse. 176 74

Previous experiments showed that transgenic mice expressing a secreted self-activating transforming growth factor (TGF) -beta1 did not show a phenotype in the lens and cornea until postnatal day 21, when anterior subcapsular cataracts, sporadic thickening of the corneal stroma, and thinning of the corneal epithelium were noted (Srinivasan et al., 1998). To examine the effects of higher concentrations of TGF-beta1 on the lens and cornea, we constructed transgenic mice harboring the strong, lens-specific chicken betaB1-crystallin promoter driving an activated porcine TGF-beta1 gene. In contrast to the earlier study, the transgenic mice had microphthalmic eyes with closed eyelids. Already at embryonic day (E) 13.5, the future cornea of the transgenic mice was threefold thicker than that of wild-type littermates due to increased proliferation of corneal stromal mesenchyme cells. Staining of fibronectin and thrombospondin-1 was increased in periocular mesenchyme. At E17.5, the thickened transgenic corneal stroma was vascularized and densely populated by abundant star-shaped, neural cell adhesion molecule-positive cells of mesenchymal appearance surrounded by irregular swirls of collagen and extracellular matrix. The corneal endothelium, anterior chamber, and stroma of iris/ciliary body did not develop, and the transgenic cornea was opaque. Fibronectin, perlecan, and thrombospondin-1 were elevated, whereas type VI collagen decreased in the transgenic corneal stroma. Stromal mesenchyme cells expressed alpha-smooth muscle actin as did lens epithelial cells and cells of the retinal pigmented epithelium. By E17.5, lens fiber cells underwent apoptotic cell death that was followed by apoptosis of the entire anterior lens epithelium between E18.5 and birth. Posteriorly, the vitreous humor was essentially absent; however, the retina appeared relatively normal. Thus, excess TGF-beta1, a mitogen for embryonic corneal mesenchyme, severely disrupts corneal and lens differentiation. Our findings profoundly contrast with the mild eye phenotype observed with presumably lower levels of ectopic TGF-beta and illustrate the complexity of TGF-beta utilization and the importance of dose when assessing the effects of this growth factor.
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PMID:Disruption of anterior segment development by TGF-beta1 overexpression in the eyes of transgenic mice. 1224 11