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Article: The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a

TitleThe mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a
Authors
Issue Date2000
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2000, v. 9 n. 5, p. 821-828 How to Cite?
AbstractExon shuffling is thought to be an important mechanism for evolution of new genes. Here we show that the mouse neurological mutation flailer (flr) expresses a novel gene that combines the promoter and first two exons of guanine nucleotide binding protein beta 5 (Gnb5) with the C-terminal exons of the closely linked Myosin 5A (MyoVA) gene (Myo5a). The flailer protein, which is expressed predominantly in brain, contains the N-terminal 83 amino acids of Gnb5 fused in-frame with the C-terminal 711 amino acids of MyoVA, including the globular tail domain that binds organelles for intracellular transport. Biochemical and genetic studies indicate that the flailer protein competes with wild-type MyoVA in vivo, preventing the localization of smooth endoplasmic reticulum vesicles in the dendritic spines of cerebellar Purkinje cells. The flailer protein thus has a dominant-negative mechanism of action with a recessive mode of inheritance due to the dependence of competitive binding on the ratio between mutant and wild-type proteins. The chromosomal arrangement of Myo5a upstream of Gnb5 is consistent with non-homologous recombination as the mutational mechanism. To our knowledge, flailer is the first example of a mammalian mutation caused by germ line exon shuffling between unrelated genes.
Persistent Identifierhttp://hdl.handle.net/10722/147455
ISSN
2015 Impact Factor: 5.985
2015 SCImago Journal Rankings: 4.288
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorJones, JMen_US
dc.contributor.authorHuang, JDen_US
dc.contributor.authorMermall, Ven_US
dc.contributor.authorHamilton, BAen_US
dc.contributor.authorMooseker, MSen_US
dc.contributor.authorEscayg, Aen_US
dc.contributor.authorCopeland, NGen_US
dc.contributor.authorJenkins, NAen_US
dc.contributor.authorMeisler, MHen_US
dc.date.accessioned2012-05-29T06:03:50Z-
dc.date.available2012-05-29T06:03:50Z-
dc.date.issued2000en_US
dc.identifier.citationHuman Molecular Genetics, 2000, v. 9 n. 5, p. 821-828en_US
dc.identifier.issn0964-6906en_US
dc.identifier.urihttp://hdl.handle.net/10722/147455-
dc.description.abstractExon shuffling is thought to be an important mechanism for evolution of new genes. Here we show that the mouse neurological mutation flailer (flr) expresses a novel gene that combines the promoter and first two exons of guanine nucleotide binding protein beta 5 (Gnb5) with the C-terminal exons of the closely linked Myosin 5A (MyoVA) gene (Myo5a). The flailer protein, which is expressed predominantly in brain, contains the N-terminal 83 amino acids of Gnb5 fused in-frame with the C-terminal 711 amino acids of MyoVA, including the globular tail domain that binds organelles for intracellular transport. Biochemical and genetic studies indicate that the flailer protein competes with wild-type MyoVA in vivo, preventing the localization of smooth endoplasmic reticulum vesicles in the dendritic spines of cerebellar Purkinje cells. The flailer protein thus has a dominant-negative mechanism of action with a recessive mode of inheritance due to the dependence of competitive binding on the ratio between mutant and wild-type proteins. The chromosomal arrangement of Myo5a upstream of Gnb5 is consistent with non-homologous recombination as the mutational mechanism. To our knowledge, flailer is the first example of a mammalian mutation caused by germ line exon shuffling between unrelated genes.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/en_US
dc.relation.ispartofHuman Molecular Geneticsen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBrain - Cytology - Metabolismen_US
dc.subject.meshDna, Complementaryen_US
dc.subject.meshExonsen_US
dc.subject.meshFungal Proteins - Geneticsen_US
dc.subject.meshGtp-Binding Protein Beta Subunitsen_US
dc.subject.meshGene Dosageen_US
dc.subject.meshGenes, Recessiveen_US
dc.subject.meshIntronsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshMice, Mutant Strainsen_US
dc.subject.meshMicroscopy, Electronen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMonomeric Gtp-Binding Proteins - Geneticsen_US
dc.subject.meshMyosin Type Ien_US
dc.subject.meshMyosins - Geneticsen_US
dc.subject.meshPurkinje Cells - Metabolism - Ultrastructureen_US
dc.subject.meshRna, Messenger - Genetics - Metabolismen_US
dc.subject.meshSaccharomyces Cerevisiae Proteinsen_US
dc.titleThe mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5aen_US
dc.typeArticleen_US
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_US
dc.identifier.authorityHuang, JD=rp00451en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1093/hmg/9.5.821-
dc.identifier.pmid10749990-
dc.identifier.scopuseid_2-s2.0-0034701252en_US
dc.identifier.hkuros51740-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034701252&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume9en_US
dc.identifier.issue5en_US
dc.identifier.spage821en_US
dc.identifier.epage828en_US
dc.identifier.isiWOS:000086177400018-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridJones, JM=7406480827en_US
dc.identifier.scopusauthoridHuang, JD=8108660600en_US
dc.identifier.scopusauthoridMermall, V=6602545621en_US
dc.identifier.scopusauthoridHamilton, BA=7202534481en_US
dc.identifier.scopusauthoridMooseker, MS=7006520381en_US
dc.identifier.scopusauthoridEscayg, A=6602849594en_US
dc.identifier.scopusauthoridCopeland, NG=35374759300en_US
dc.identifier.scopusauthoridJenkins, NA=35379887700en_US
dc.identifier.scopusauthoridMeisler, MH=7005904665en_US

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