Tissue-specific changes in the hydroxylysine content and cross-links of collagens and alterations in fibril morphology in lysyl hydroxylase 1 knock-out mice
| Autor: | Johanna Myllyharju, Raija Soininen, Ruud A. Bank, Marjo Hyry, Kati Takaluoma, Raija Sormunen, Juha Lantto, Kari I. Kivirikko |
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| Přispěvatelé: | Orale Celbiologie (OUD, ACTA) |
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Connective tissue Mice Inbred Strains Biochemistry Hydroxylysine Skin Diseases Extracellular matrix chemistry.chemical_compound Mice In vivo Internal medicine medicine.artery medicine Animals Tissue Distribution Molecular Biology Gait Mice Knockout Aorta Muscular hypotonia Procollagen-Lysine 2-Oxoglutarate 5-Dioxygenase Wild type Cell Biology Anatomy Tendon Disease Models Animal medicine.anatomical_structure Endocrinology Phenotype chemistry Muscle Hypotonia Ehlers-Danlos Syndrome Collagen |
| Zdroj: | The Journal of Biological Chemistry, 282, 6588-6596. American Society for Biochemistry and Molecular Biology Inc. Takaluoma, K, Hyry, M, Lantto, J, Sormunen, R, Bank, R A, Kivirikko, K I, Myllyharja, J & Soininen, R 2007, ' Tissue-specific changes in the hydroxylysine content and cross-links of collagens and alterations in fibril morphology in lysyl hydroxylase 1 knock-out mice ', The Journal of Biological Chemistry, vol. 282, pp. 6588-6596 . https://doi.org/10.1074/jbc.M608830200 |
| ISSN: | 1083-351X 0021-9258 |
| DOI: | 10.1074/jbc.M608830200 |
| Popis: | We have generated mice with targeted inactivation of the Plod1 gene for lysyl hydroxylase 1 (LH1). Its human mutations cause Ehlers-Danlos syndrome VIA (EDS VIA) characterized by muscular hypotonia, joint laxity, and kyphoscoliosis. The Plod1(-/-) mice are flaccid and have gait abnormalities. About 15% of them died because of aortic rupture and smooth muscle cells in non-ruptured Plod1(-/-) aortas showed degenerative changes. Collagen fibrils in the Plod1(-/-) aorta and skin had an abnormal morphology. The LH activity level in the Plod1(-/-) skin and aorta samples was 35-45% of that in the wild type. The hydroxylysine content was decreased in all the Plod1(-/-) tissues, ranging from 22% of that in the wild type in the skin to 75 and 86% in the femur and lung. The hydroxylysylpyridinoline crosslinks likewise showed decreases in all the Plod1(-/-) tissues, ranging from 28 and 33% of that in the wild type in the aorta and cornea to 47 and 59% in femur and tendon, while lysylpyridinolines were increased. The hydroxylysines found in the Plod1(-/-) collagens and their cross-links were evidently synthesized by the other two LH isoenzymes. Few data are available on abnormalities in EDS VIA tissues other than the skin. Plod1(-/-) mice offer an in vivo model for systematic analysis of the tissue-specific consequences of the lack of LH1 activity and may also provide a tool for analyzing the roles of connective tissue in muscle function and the complex interactions occurring in the proper assembly of the extracellular matrix. |
| Databáze: | OpenAIRE |
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