Comparison of Phenotypes between Different \(vangl2\) Mutants Demonstrates Dominant Effects of the \(Looptail\) Mutation during Hair Cell Development

DSpace/Manakin Repository

Comparison of Phenotypes between Different \(vangl2\) Mutants Demonstrates Dominant Effects of the \(Looptail\) Mutation during Hair Cell Development

Show simple item record

dc.contributor.author Yin, Haifeng
dc.contributor.author Copley, Catherine O.
dc.contributor.author Deans, Michael R.
dc.contributor.author Goodrich, Lisa V.
dc.date.accessioned 2012-04-26T18:05:39Z
dc.date.issued 2012
dc.identifier.citation Yin, Haifeng, Catherine O. Copley, Lisa V. Goodrich, and Michael R. Deans. 2012. Comparison of phenotypes between different \(vangl2\) mutants demonstrates dominant effects of the \(Looptail\) mutation during hair cell development. PLoS ONE 7(2): e31988. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8623557
dc.description.abstract Experiments utilizing the \(Looptail\) mutant mouse, which harbors a missense mutation in the \(vangl2\) gene, have been essential for studies of planar polarity and linking the function of the core planar cell polarity proteins to other developmental signals. Originally described as having dominant phenotypic traits, the molecular interactions underlying the \(Looptail\) mutant phenotype are unclear because Vangl2 protein levels are significantly reduced or absent from mutant tissues. Here we introduce a \(vangl2\) knockout mouse and directly compare the severity of the knockout and \(Looptail\) mutant phenotypes by intercrossing the two lines and assaying the planar polarity of inner ear hair cells. Overall the \(vangl2\) knockout phenotype is milder than the phenotype of compound mutants carrying both the \(Looptail\) and \(vangl2\) knockout alleles. In compound mutants a greater number of hair cells are affected and changes in the orientation of individual hair cells are greater when quantified. We further demonstrate in a heterologous cell system that the protein encoded by the Looptail mutation \((Vangl2^{S464N})\) disrupts delivery of Vangl1 and Vangl2 proteins to the cell surface as a result of oligomer formation between Vangl1 and \(Vangl2^{S464N}\), or Vangl2 and \(Vangl2^{S464N}\), coupled to the intracellular retention of \(Vangl2^{S464N}\). As a result, Vangl1 protein is missing from the apical cell surface of vestibular hair cells in \(Looptail\) mutants, but is retained at the apical cell surface of hair cells in \(vangl2\) knockouts. Similarly the distribution of Prickle-like2, a putative Vangl2 interacting protein, is differentially affected in the two mutant lines. In summary, we provide evidence for a direct physical interaction between Vangl1 and Vangl2 through a combination of in vitro and in vivo approaches and propose that this interaction underlies the dominant phenotypic traits associated with the \(Looptail\) mutation. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0031988 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282788/pdf/ en_US
dash.license LAA
dc.subject biology en_US
dc.subject developmental biology en_US
dc.subject genetics en_US
dc.subject genetic mutation en_US
dc.subject model organisms en_US
dc.subject animal models en_US
dc.subject neuroscience en_US
dc.subject cellular neuroscience en_US
dc.subject medicine en_US
dc.subject otorhinolaryngology en_US
dc.title Comparison of Phenotypes between Different \(vangl2\) Mutants Demonstrates Dominant Effects of the \(Looptail\) Mutation during Hair Cell Development en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Goodrich, Lisa V.
dc.date.available 2012-04-26T18:05:39Z

Files in this item

Files Size Format View
3282788.pdf 3.826Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record

 
 

Search DASH


Advanced Search
 
 

Submitters