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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because the organogenesis and physiology of the lens are essentially similar in various mammals, an understanding of the etiology and pathogenesis of the formation of cataract in an animal model will enhance our knowledge of cataractogenesis in man. In this review, we summarize the background, etiology, and pathogenesis of cataracts that occur in rodents. The main advantages of using rodent mutants include the well-researched genetics of the animals and the comparative ease of breeding of large litters. Numerous rodent models of congenital and hereditary cataracts have been studied extensively. In mice, the models include the Cts strain, Fraser mouse, lens opacity gene (Lop) strain, Lop-2 and Lop-3 strains, Philly mouse, Nakano mouse, Nop strain, Deer mouse, Emory mouse, Swiss Webster strain, Balb/c-nct/nct mouse, and SAM-R/3 strain. The rat models include BUdR, ICR, Sprague-Dawley, and Wistar rats, the spontaneously hypertensive rat (SHR), the John Rapp inbred strain of Dahl salt-sensitive rat, as well as WBN/Kob, Royal College of Surgeons (RCS), and Brown-Norway rats. Other proposed models for the study of hereditary cataract include the degu and the guinea pig. Because of the ease of making clinical observations in vivo and the subsequent availability of the intact lens for laboratory analyses at different stages of cataract formation, these animals provide excellent models for clinicopathologic correlations, for monitoring of the natural history of the aging process and of metabolic defects, as well as for investigations on the effect of cataract-modulating agents and drugs, including the prospect of gene therapy.
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PMID:Rodent models of congenital and hereditary cataract in man. 195 36

The cataract produced by the dominant Cat Fraser gene in mouse is associated with quantitative changes in lens proteins (crystallin) and with capsule abnormalities. We have analyzed and compared the protein synthesis in control and mutant lenses using [3H]leucine and [3H]proline incorporation. The specific activities of free [3H]leucine in the intracellular pools of the two mouse strains were identical, while the incorporation of both labelled amino acids in proteins was largely increased in Cat Fraser lens. These data indicate that the higher labelling of Cat Fraser lens proteins reflects a true change in the cellular synthesis activity by Cat Fraser lens cells. Despite the enhanced type IV collagen synthesis by Cat Fraser epithelial cells, the amount of type IV collagen in Cat Fraser capsule is lower than in control. This altered type-IV collagen metabolism may disturb the structure of Cat Fraser capsule which becomes thicker.
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PMID:Analysis of lens protein synthesis in a cataractous mutant mouse: the Cat Fraser. 224 25

Quantification and biosynthesis of type I and type III collagens were determined in skin of control and Fraser mice (CatFraser mutation), which exhibit a genetically determined cataract. Skin organ cultures were labelled with [3H]proline. Pepsin-solubilized collagens were studied using three different approaches: (a) differential salt precipitation at neutral pH, followed by SDS-polyacrylamide gel electrophoresis; (b) differential salt precipitation at acid pH followed by SDS-polyacrylamide gel electrophoresis. (c) CNBr peptide analysis. These methods gave consistent and reproducible results, indicating a selective decrease of type I collagen in Fraser mouse skin as compared to control mouse skin. Metabolic labelling of skin organ cultures showed a decreased specific radioactivity of hydroxy[3H]proline in type I collagen of Fraser mouse skin. The concordant results of these experiments suggest a genetically determined alteration of interstitial collagen metabolism in the Fraser mutation apparently specifically concerning the expression of type I collagen gene(s).
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PMID:Selective decrease of type I collagen synthesis in Fraser mice skin. 393 69

The eye lens of the Fraser mouse contains a dominantly inherited cataract with reduced amounts of seven distinct but homologous gamma crystallins encoded by a family of gamma-crystallin genes. The results of experiments with cultured lenses, cell-free RNA translation, and Northern blot hybridization indicated a specific loss of the family of gamma-crystallin messenger RNA's in the Fraser mouse lens. Southern blot hybridization of genomic DNA's from normal and Fraser mice showed no differences in gamma-crystallin coding sequences.
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PMID:Selective loss of a family of gene transcripts in a hereditary murine cataract. 396 60

In the evaluation of the genetic heterogeneity of congenital cataract and in establishing the nosologic diagnosis the cooperation of the ophthalmologist and geneticist is necessary. The importance of ophthalmologic syndromology for genetic counseling is shown in cases of Fraser's syndrome (McKusick No. 21,900), Usher's syndrome (N. 27,690), a syndrome involving acromegaly, cutis verticis gyrata and corneal leukoma (No. 10,210), a syndrome with congenital cataract, microphthalmia and nystagmus (No. 21,255), and a presumably new dominant hereditary cataract-vitiligo syndrome.
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PMID:Genetic counseling in congenital eye disorders. 641 63

The immunohistochemical method was used to study lens formation in a new dominant mouse strain with a small eye and lens cataract (gene symbol Cs). Antisera to pure alpha- and gamma-crystallins were used. In the homozygotes, the eyes have cataractous lenses about half the size of normal lenses. In the heterozygotes, the eyes show opacities of the lens but the lens itself is normal in size. The mouse strain has two genes in the same autosome which cause the phenogenetical characteristics of small eyes and cataracts. One reflects the defect of the gamma-crystallin synthesis in the secondary lens fibers in the equatorial zone. This is a recessive gene and it may cause the small lens. The other gene is responsible for the swollen, granular and misshaped fiber cells. This is a dominant gene like that in the Fraser's cataract and it may cause the cataract lens.
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PMID:An immunohistochemical study of lens development in a mutant small eye and cataractous mouse. 679 32

The major intrinsic protein (MIP) of the vertebrate eye lens is the first identified member of a sequence-related family of cell-membrane proteins that appears to have evolved by gene duplication. Several members of the MIP family transport water (aquaporins), glycerol and other small molecules in microbial, plant and animal cells. Mutations in two aquaporin homologues of MIP underlie an autosomal recessive form of nephrogenic diabetes insipidus and absence of the Colton blood group antigens in humans, whereas, mutation of a third MIP-like gene underlies 'big brain' development in Drosophila. Here we show that distinct mutations in the murine Mip gene underlie one form of autosomal dominant cataract in the mouse. The cataract Fraser mutation is a transposon-induced splicing error that substitutes a long terminal repeat sequence for the carboxy-terminus of MIP. The lens opacity mutation is an amino-acid substitution that inhibits targeting of MIP to the cell-membrane. These allelic cataract mutations provide the first direct evidence that MIP plays a crucial role in the development of a transparent eye lens.
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PMID:Mutations in the founder of the MIP gene family underlie cataract development in the mouse. 856 64

Aquaporin-0 (AQP0) is the major intrinsic protein of lens fiber cells and the founder member of the water channel gene family. Here we show that disruption of the AQP0 gene by an early transposon (ETn) element results in expression of a chimeric protein, comprised of approximately 75% AQP0 and approximately 25% ETn long terminal repeat (LTR) sequence, in the cataract Fraser (CatFr) mouse lens. Immunoblot analysis showed that mutant AQP0-LTR was similar in mass to wild-type AQP0. However, immunofluorescence microscopy revealed that AQP0-LTR was localized to intracellular membranes rather than to plasma membranes of lens fiber cells. Heterozygous CatFr lenses were similar in size to wild-type but displayed abnormal regions of translucence and light scattering. Scanning electron microscopy further revealed that mature fiber cells within the core of the heterozygous CatFr lens failed to stratify into uniform, concentric growth shells, suggesting that the AQP0 water channel facilitates the development of the unique cellular architecture of the crystalline lens.
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PMID:Disruption of lens fiber cell architecture in mice expressing a chimeric AQP0-LTR protein. 1105 41

Aquaporin 0 (AQP0) is the major intrinsic protein of the lens and its water permeability can be modulated by changes in pH and Ca2+. The Cataract Fraser (Cat Fr) mouse accumulates an aberrant AQP0 (AQP0-LTR) in sub-cellular compartments resulting in a congenital cataract. We investigated the interference of AQP0-LTR with normal function of AQP0 in three systems. First, we created a transgenic mouse expressing AQP0 and AQP0-LTR in the lens. Expression of AQP0 did not prevent the congenital cataract but improved the size and transparency of the lens. Second, we measured water permeability of AQP0 co-expressed with AQP0-LTR in Xenopus oocytes. A low expression level of AQP0-LTR decreased the water permeability of AQP0, and a high expression level eliminated its calcium regulation. Third, we studied trafficking of AQP0 and AQP0-LTR in transfected lens epithelial cells. At low expression level, AQP0-LTR migrated with AQP0 toward the cell membrane, but at high expression level, it accumulated in sub-cellular compartments. The deleterious effect of AQP0-LTR on lens development may be explained by lowering water permeability and abolishing calcium regulation of AQP0. This study provides the first evidence that calcium regulation of AQP0 water permeability may be crucial for maintaining normal lens homeostasis and development.
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PMID:AQP0-LTR of the Cat Fr mouse alters water permeability and calcium regulation of wild type AQP0. 1651 71