comparison of phenotypes between different vangl2 mutants demonstrates dominant effects of the looptail mutation during hair cell development比较不同vangl2之间的表型变异表明主导looptail突变在毛细胞发育的影响.pdf

Comparison of Phenotypes between Different vangl2 Mutants Demonstrates Dominant Effects of the Looptail Mutation during Hair Cell Development 1 1 2 1 Haifeng Yin , Catherine O. Copley , Lisa V. Goodrich , Michael R. Deans * 1The Departments of Neuroscience and Otolaryngology-Head and Neck Surgery, the Center for Hearing and Balance and the Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 2 The Department of Neurobiology, Harvard Medical School, Boston, Maryland, United States of America 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 (Vangl2S464N) disrupts delivery of Vangl1 and Vangl2 proteins to