title: A recessive mutation leading to vertebral ankylosis in zebrafish is associated with amino acid alterations in the homologue of the human membrane-associated guanylate kinase DLG3.
abstract: We describe the characterization of the zebrafish homologue of the human gene DLG3. The zebrafish dlg3 gene encodes a membrane-associated guanylate kinase containing a single PDZ domain. This gene was cloned using a gene-trap construct inserted in the gene's first intron. The insertion co-segregates with a viable mutation called humpback (hmp), which leads to formation of ankylotic vertebrae in adult fishes. Insertion and mutation have both been mapped to chromosome 12, in a segment which is syntenic with region p12 to q12 of human chromosome 17. The hmp mutant phenotype, however, appears to be due to two point mutations in the guanylate kinase domain rather than to the transgene insertion itself. The results of this study are discussed in the light of the possible function of the guanylate kinase domain.
authors.affiliation: Institut für Entwicklungsbiologie, Universität zu Köln, 50923 Köln, Germany.
authors.forename: C
authors.initials: C
authors.lastname: König
authors.forename: Y L
authors.initials: YL
authors.lastname: Yan
authors.forename: J
authors.initials: J
authors.lastname: Postlethwait
authors.forename: S
authors.initials: S
authors.lastname: Wendler
authors.forename: J A
authors.initials: JA
authors.lastname: Campos-Ortega
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000844:Ankylosis / Q000235:genetics* / Q000662:veterinary; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004251:DNA Transposable Elements; D005393:Fish Diseases / Q000235:genetics*; D005808:Genes, Recessive; D051528:Guanylate Kinases; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins; D013131:Spine / Q000002:abnormalities*; D014158:Transcription, Genetic; D019076:Transgenes; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins; D062826:Zonula Occludens-1 Protein
chemical_list: C496470:DLG3 protein, zebrafish; D004251:DNA Transposable Elements; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D029961:Zebrafish Proteins; D062826:Zonula Occludens-1 Protein; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases