title: Zebrafish mutants with disrupted early T-cell and thymus development identified in early pressure screen.
abstract: Generation of mature T lymphocytes requires an intact hematopoietic stem cell compartment and functional thymic epithelium. We used the zebrafish (Danio rerio) to isolate mutations that affect the earliest steps in T lymphopoiesis and thymic organogenesis. Here we describe the results of a genetic screen in which gynogenetic diploid offspring from heterozygous females were analyzed by whole-mount in situ hybridization for the expression of rag-1. To assess immediately if a global defect in hematopoiesis resulted in the mutant phenotype, alpha-embryonic globin expression was simultaneously assayed for multilineage defects. In this report, we present the results obtained with this strategy and show representative mutant phenotypes affecting early steps in T-cell development and/or thymic epithelial cell development. We discuss the advantage of this strategy and the general usefulness of the zebrafish as a model system for vertebrate lymphopoiesis and thymic organogenesis.
authors: Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA. nikolaus.trede@hci.utah.edu
authors: Nikolaus S
authors: NS
authors: Trede
authors: Tatsuya
authors: T
authors: Ota
authors: Hirohide
authors: H
authors: Kawasaki
authors: Barry H
authors: BH
authors: Paw
authors: Tammisty
authors: T
authors: Katz
authors: Bradley
authors: B
authors: Demarest
authors: Sarah
authors: S
authors: Hutchinson
authors: Yi
authors: Y
authors: Zhou
authors: Candace
authors: C
authors: Hersey
authors: Agustin
authors: A
authors: Zapata
authors: Chris T
authors: CT
authors: Amemiya
authors: Leonard I
authors: LI
authors: Zon
mesh_terms: D000818:Animals; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D051740:Ikaros Transcription Factor / Q000235:genetics; D017403:In Situ Hybridization; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D051858:Forkhead Transcription Factors; C474191:Foxn1 protein, zebrafish; D018398:Homeodomain Proteins; D029961:Zebrafish Proteins; C497240:ikzf1 protein, zebrafish; C064658:RAG-1 protein; D051740:Ikaros Transcription Factor