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Conference Paper: Unfolded protein response leading to cataractogenesis in a microphthalmia cataract mouse mutant

TitleUnfolded protein response leading to cataractogenesis in a microphthalmia cataract mouse mutant
Authors
Issue Date2009
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/modo
Citation
The 16th International Society of Developmental Biologists Congress, Edinburgh, Scotland, 6-10 September 2009. How to Cite?
AbstractCongenital cataract is a leading cause of visual disability among children worldwide, it has a heterogeneous genetic basis but the cellular and molecular bases for cataractogenesis remain elusive. In our laboratory we have a spontaneously occurring, autosomal dominant mouse mutant named Secc, which displays combined features of small eye, cataract and closed eyelid. By mapping and sequencing we identified a single point deletion at nucleotide 273 of the Cryga gene, leading to a frame-shift from the 3rd Greek Key motif of the gamma-A-crystallin. Cataract features were initiated in E14.5 Secc mutant, the nuclei of the primary lens fibres were scattered and failed to align in the equatorial region. By E16.5, the secondary lens fibre cells were abnormally arranged with poor lens suture formation. Apoptotic cells were found in the centre of the lens as shown by TUNEL assay, the cytoskeleton and cell adhesion in the lens centre were disturbed as shown in immunohistochemistry analysis. By western blotting we found that mutant gamma-crystallins were reduced in amount and enriched in the insoluble fraction, suggesting that mutant gamma-a-crystallins were misfolded and protein aggregates were formed. We found that the expression of genes involved in the unfolded protein response (UPR) pathways including BiP, CHOP and spliced variant of XBP-1 were all up-regulated significantly in E14.5 and 16.5 mutant lenses. Therefore, the mutant gamma-A-crystallin appeared to trigger UPR and cell death in the fibre cells. The mutant cells lost their normal cell adhesion, failed to maintain the proper lens architecture, leading to cataract formation.
DescriptionMechanisms of Development, 2009, v. 126, suppl. 1, p. S128-S129
Persistent Identifierhttp://hdl.handle.net/10722/96327
ISSN
2015 Impact Factor: 2.041
2015 SCImago Journal Rankings: 1.368
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTam, CNen_HK
dc.contributor.authorCheng, MHen_HK
dc.contributor.authorTsang, SLen_HK
dc.contributor.authorYam, GHFen_HK
dc.contributor.authorPang, CPen_HK
dc.contributor.authorSham, MHen_HK
dc.date.accessioned2010-09-25T16:30:23Z-
dc.date.available2010-09-25T16:30:23Z-
dc.date.issued2009en_HK
dc.identifier.citationThe 16th International Society of Developmental Biologists Congress, Edinburgh, Scotland, 6-10 September 2009.-
dc.identifier.issn0925-4773-
dc.identifier.urihttp://hdl.handle.net/10722/96327-
dc.descriptionMechanisms of Development, 2009, v. 126, suppl. 1, p. S128-S129-
dc.description.abstractCongenital cataract is a leading cause of visual disability among children worldwide, it has a heterogeneous genetic basis but the cellular and molecular bases for cataractogenesis remain elusive. In our laboratory we have a spontaneously occurring, autosomal dominant mouse mutant named Secc, which displays combined features of small eye, cataract and closed eyelid. By mapping and sequencing we identified a single point deletion at nucleotide 273 of the Cryga gene, leading to a frame-shift from the 3rd Greek Key motif of the gamma-A-crystallin. Cataract features were initiated in E14.5 Secc mutant, the nuclei of the primary lens fibres were scattered and failed to align in the equatorial region. By E16.5, the secondary lens fibre cells were abnormally arranged with poor lens suture formation. Apoptotic cells were found in the centre of the lens as shown by TUNEL assay, the cytoskeleton and cell adhesion in the lens centre were disturbed as shown in immunohistochemistry analysis. By western blotting we found that mutant gamma-crystallins were reduced in amount and enriched in the insoluble fraction, suggesting that mutant gamma-a-crystallins were misfolded and protein aggregates were formed. We found that the expression of genes involved in the unfolded protein response (UPR) pathways including BiP, CHOP and spliced variant of XBP-1 were all up-regulated significantly in E14.5 and 16.5 mutant lenses. Therefore, the mutant gamma-A-crystallin appeared to trigger UPR and cell death in the fibre cells. The mutant cells lost their normal cell adhesion, failed to maintain the proper lens architecture, leading to cataract formation.-
dc.languageengen_HK
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/modo-
dc.relation.ispartofInternational Society of Developmental Biologists Congressen_HK
dc.titleUnfolded protein response leading to cataractogenesis in a microphthalmia cataract mouse mutanten_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0925-4773&volume=126, suppl. 1&spage=S128&epage=S129&date=2009&atitle=Unfolded+protein+response+leading+to+cataractogenesis+in+a+microphthalmia+cataract+mouse+mutant-
dc.identifier.emailTam, CN: tcnjoanne@gmail.comen_HK
dc.identifier.emailCheng, MH: h0594183@hkusua.hku.hken_HK
dc.identifier.emailTsang, SL: sltsang@HKUSUA.hku.hken_HK
dc.identifier.emailSham, MH: mhsham@hkucc.hku.hken_HK
dc.identifier.doi10.1016/j.mod.2009.06.256-
dc.identifier.hkuros168660en_HK
dc.identifier.volume126, suppl. 1-
dc.identifier.spageS128-
dc.identifier.epageS129-
dc.identifier.isiWOS:000270034900360-

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