title: A novel hypomorphic Looptail allele at the planar cell polarity Vangl2 gene.
abstract: Vangl2 forms part of the planar cell polarity signalling pathway and is the gene defective in the Looptail (Lp) mouse mutant. Two previously described alleles, Lp and Lp(m1Jus) , segregate in a semi-dominant fashion, with heterozygotes displaying the looped-tail appearance, while homozygotes show the neural tube defect called craniorachischisis. Here, we report a novel experimentally induced allele, Lp(m2Jus) , that carries a missense mutation, R259L, in Vangl2. This mutation was specific to the Lp phenotype and absent from both parental strains and 28 other inbred strains. Notably, this mutation segregates in a recessive manner with all heterozygotes appearing normal and 47% of homozygotes showing a looped-tail. Homozygous Lp(m2Jus) embryos showed spina bifida in 12%. Lp(m2Jus) genetically interacts with Lp with 77% of compound heterozygotes displaying craniorachischisis. Vangl2(R259L) behaved like the wild-type allele in overexpression and morpholino knockdown/rescue assays in zebrafish embryos. These data suggest that Lp(m2Jus) represents a new hypomorphic allele of Lp.
authors.affiliation: Department of Obstetrics and Gynecology, CHU Sainte Justine Research Center and University of Montreal, Montreal, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guyot
authors.forename: Ciprian M
authors.initials: CM
authors.lastname: Bosoi
authors.forename: Fares
authors.initials: F
authors.lastname: Kharfallah
authors.forename: Annie
authors.initials: A
authors.lastname: Reynolds
authors.forename: Pierre
authors.initials: P
authors.lastname: Drapeau
authors.forename: Monica
authors.initials: M
authors.lastname: Justice
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
authors.forename: Zoha
authors.initials: Z
authors.lastname: Kibar
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics*; D016764:Cell Polarity / Q000235:genetics*; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D054928:Validation Studies as Topic; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology
chemical_list: C431577:Ltap protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D029961:Zebrafish Proteins; C491759:vangl2 protein, zebrafish