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Article: Multiexon deletions in the type I collagen COL1A2 gene in osteogenesis imperfecta type IB. Molecules containing the shortened α2(I) chains show differential incorporation into the bone and skin extracellular matrix

TitleMultiexon deletions in the type I collagen COL1A2 gene in osteogenesis imperfecta type IB. Molecules containing the shortened α2(I) chains show differential incorporation into the bone and skin extracellular matrix
Authors
Issue Date1996
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1996, v. 271 n. 35, p. 21068-21074 How to Cite?
AbstractOsteogenesis imperfecta (OI) type IB is a rare subset of the mildest form of OI, clinically characterized by moderate bone fragility, blue sclera, and dentinogenesis imperfecta. Cultured skin fibroblasts from two unrelated individuals (OI-197 and OI-165) with the typical features of OI type IB produced shortened α2(I) chains. Reverse transcription-polymerase chain reaction of the α2(I)-cDNA revealed deletions in the triple helical domain of 5 exons (exons 7-11) in OI-197, and 8 exons (exons 10-17) in OI-165. This exon skipping was caused by genomic deletions in one allele of COL1A2 with the breakpoints located in introns 6 and 11 in OI-197, and introns 9 and 17 in OI-165. The secretion and deposition of the mutant collagen into the matrix was measured in vitro in cultures of skin fibroblasts and bone osteoblasts, grown in the presence of ascorbic acid to induce collagen matrix formation and maturation, as well as in collagen extracts from skin and bone. The secretion of mutant collagen was impaired and long term cultures of fibroblasts showed that the mutant collagen was not incorporated into the mature collagenous matrix produced in vitro by skin fibroblasts from both patients. Likewise, the shortened α2(I) chain was not demonstrable in skin extracts. In contrast, bone extracts from OI-197 showed the presence of the mutant collagen. This incorporation of the abnormal collagen into the mature matrix was also demonstrated in long term cultures of the patient's osteoblasts. The deposition of the mutant collagen by bone osteoblasts but not by skin fibroblasts demonstrates a tissue specificity in the incorporation of mutant collagen into the matrix which may explain the primary involvement of bone and not skin in these patients.
Persistent Identifierhttp://hdl.handle.net/10722/147404
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMundlos, Sen_US
dc.contributor.authorChan, Den_US
dc.contributor.authorWeng, YMen_US
dc.contributor.authorSillence, DOen_US
dc.contributor.authorCole, WGen_US
dc.contributor.authorBateman, JFen_US
dc.date.accessioned2012-05-29T06:03:29Z-
dc.date.available2012-05-29T06:03:29Z-
dc.date.issued1996en_US
dc.identifier.citationJournal Of Biological Chemistry, 1996, v. 271 n. 35, p. 21068-21074en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/147404-
dc.description.abstractOsteogenesis imperfecta (OI) type IB is a rare subset of the mildest form of OI, clinically characterized by moderate bone fragility, blue sclera, and dentinogenesis imperfecta. Cultured skin fibroblasts from two unrelated individuals (OI-197 and OI-165) with the typical features of OI type IB produced shortened α2(I) chains. Reverse transcription-polymerase chain reaction of the α2(I)-cDNA revealed deletions in the triple helical domain of 5 exons (exons 7-11) in OI-197, and 8 exons (exons 10-17) in OI-165. This exon skipping was caused by genomic deletions in one allele of COL1A2 with the breakpoints located in introns 6 and 11 in OI-197, and introns 9 and 17 in OI-165. The secretion and deposition of the mutant collagen into the matrix was measured in vitro in cultures of skin fibroblasts and bone osteoblasts, grown in the presence of ascorbic acid to induce collagen matrix formation and maturation, as well as in collagen extracts from skin and bone. The secretion of mutant collagen was impaired and long term cultures of fibroblasts showed that the mutant collagen was not incorporated into the mature collagenous matrix produced in vitro by skin fibroblasts from both patients. Likewise, the shortened α2(I) chain was not demonstrable in skin extracts. In contrast, bone extracts from OI-197 showed the presence of the mutant collagen. This incorporation of the abnormal collagen into the mature matrix was also demonstrated in long term cultures of the patient's osteoblasts. The deposition of the mutant collagen by bone osteoblasts but not by skin fibroblasts demonstrates a tissue specificity in the incorporation of mutant collagen into the matrix which may explain the primary involvement of bone and not skin in these patients.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBone And Bones - Metabolismen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshChilden_US
dc.subject.meshCollagen - Genetics - Metabolismen_US
dc.subject.meshDna, Complementaryen_US
dc.subject.meshExonsen_US
dc.subject.meshExtracellular Matrix - Metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutationen_US
dc.subject.meshOsteogenesis Imperfecta - Genetics - Pathologyen_US
dc.subject.meshSequence Deletionen_US
dc.subject.meshSkin - Metabolismen_US
dc.titleMultiexon deletions in the type I collagen COL1A2 gene in osteogenesis imperfecta type IB. Molecules containing the shortened α2(I) chains show differential incorporation into the bone and skin extracellular matrixen_US
dc.typeArticleen_US
dc.identifier.emailChan, D:chand@hkucc.hku.hken_US
dc.identifier.authorityChan, D=rp00540en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.271.35.21068en_US
dc.identifier.pmid8702873-
dc.identifier.scopuseid_2-s2.0-0029787444en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0029787444&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume271en_US
dc.identifier.issue35en_US
dc.identifier.spage21068en_US
dc.identifier.epage21074en_US
dc.identifier.isiWOS:A1996VE47700019-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridMundlos, S=7005248176en_US
dc.identifier.scopusauthoridChan, D=7402216545en_US
dc.identifier.scopusauthoridWeng, YM=36916958800en_US
dc.identifier.scopusauthoridSillence, DO=7006527427en_US
dc.identifier.scopusauthoridCole, WG=7201518727en_US
dc.identifier.scopusauthoridBateman, JF=16135557700en_US

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