Abstract:
:We have generated transgenic mice harboring a glycine-to-cysteine mutation in residue 85 of the triple helical domain of mouse type II collagen. The offspring of different founders displayed a phenotype of severe chondrodysplasia characterized by short limbs and trunk, cranio-facial deformities, and cleft palate. The affected pups died of acute respiratory distress caused by an inability to inflate lungs at birth. Staining of the skeleton showed a severe retardation of growth for practically all bones. Light microscopic examination indicated a decrease in cartilage matrix density, a severe disorganization of growth plate architecture, and the presence of streaks of fibrillar material in the cartilage matrix. Electron microscopic analysis showed a pronounced decrease in the number of typical thin cartilage collagen fibrils, distension of the rough endoplasmic reticulum of chondrocytes, and the presence of abnormally large banded collagen fibril bundles. The level of expression of the mutant type II procollagen alpha 1 chain transgene in cartilage tissues was approximately equal to that of the endogenous gene in two of the strains. We propose that the principal consequence of the mutation is a considerable reduction in density of the typical thin cartilage collagen fibrils and that this phenomenon causes the severe disorganization of the growth plate. We also postulate that the abnormal thick collagen fibrils are probably related to a defect in crosslinking between the collagen molecules. The cartilage anomalies displayed by these transgenic mice are remarkably similar to those of certain human chondrodysplasias.
journal_name
Proc Natl Acad Sci U S Aauthors
Garofalo S,Vuorio E,Metsaranta M,Rosati R,Toman D,Vaughan J,Lozano G,Mayne R,Ellard J,Horton Wdoi
10.1073/pnas.88.21.9648subject
Has Abstract,Author List Incompletepub_date
1991-11-01 00:00:00pages
9648-52issue
21eissn
0027-8424issn
1091-6490journal_volume
88pub_type
杂志文章abstract::The TFIID transcription initiation complex is composed of TBP and multiple TAFs. Studies in unicellular systems indicate that TAF250 is required for progression through G(1)/S of the cell cycle and repression of apoptosis. Here we extend these in vivo studies by determining the developmental requirements for TAF250 in...
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doi:10.1073/pnas.97.3.1154
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2008-12-02 00:00:00
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更新日期:2003-12-23 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2017-01-03 00:00:00