title: Defective adgra2 (gpr124) splicing and function in zebrafish ouchless mutants.
abstract: A hitherto unidentified N-ethyl-N-nitrosourea (ENU)-induced mutation affects dorsal root ganglia (DRG) formation in ouchless mutant zebrafish larvae. In contrast to previous findings assigning the ouchless phenotypes to downregulated sorbs3 transcript levels, this work re-attributes the phenotypes to an essential splice site mutation affecting adgra2 (gpr124) splicing and function. Accordingly, ouchless mutants fail to complement previously characterized adgra2 mutants and exhibit highly penetrant cerebrovascular defects. The aberrantly spliced adgra2 transcript found in ouchless mutants encodes a receptor lacking a single leucine-rich repeat (LRR) within its N-terminus.
authors.affiliation: Laboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
authors.forename: Naguissa
authors.initials: N
authors.lastname: Bostaille
authors.affiliation: Laboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Gauquier
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Didier Y R
authors.initials: DY
authors.lastname: Stainier
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Raible
authors.affiliation: Laboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles (ULB), B-6041 Gosselies, Belgium Benoit.Vanhollebeke@ulb.ac.be.|Center for Microscopy and Molecular Imaging, Université libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
authors.forename: Benoit
authors.identifier: 0000-0002-0353-365X
authors.initials: B
authors.lastname: Vanhollebeke
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002561:Cerebrovascular Disorders / Q000196:embryology / Q000235:genetics; D004625:Embryo, Nonmammalian; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics; D009154:Mutation; D009421:Nervous System Malformations / Q000235:genetics; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: D043562:Receptors, G-Protein-Coupled; D029961:Zebrafish Proteins; C000605631:adgra2 protein, zebrafish
keywords: Blood–brain barrier; Zebrafish; adgra2; gpr124; ouchless; reck; sorbs3