title: A mutation in a chromosome condensin II subunit, kleisin beta, specifically disrupts T cell development.
abstract: Condensins are ubiquitously expressed multiprotein complexes that are important for chromosome condensation and epigenetic regulation of gene transcription, but whose specific roles in vertebrates are poorly understood. We describe a mouse strain, nessy, isolated during an ethylnitrosourea screen for recessive immunological mutations. The nessy mouse has a defect in T lymphocyte development that decreases circulating T cell numbers, increases their expression of the activation/memory marker CD44, and dramatically decreases the numbers of CD4(+)CD8(+) thymocytes and their immediate DN4 precursors. A missense mutation in an unusual alternatively spliced first exon of the kleisin beta gene, a member of the condensin II complex, was shown to be responsible and act in a T cell-autonomous manner. Despite the ubiquitous expression and role of condensins, kleisin beta(nes/nes) mice were viable, fertile, and showed no defects even in the parallel pathway of B cell lymphocyte differentiation. These data define a unique lineage-specific requirement for kleisin beta in mammalian T cell differentiation.
authors.affiliation: School of Biochemistry and Molecular Biology, John Curtin School of Medical Research, and Australian Phenomics Facility, Australian National University, Canberra ACT 0200, Australia.
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Gosling
authors.forename: Lydia E
authors.initials: LE
authors.lastname: Makaroff
authors.forename: Angelo
authors.initials: A
authors.lastname: Theodoratos
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Belinda
authors.initials: B
authors.lastname: Whittle
authors.forename: Lixin
authors.initials: L
authors.lastname: Rui
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Hong
authors.forename: Gavin C
authors.initials: GC
authors.lastname: Kennedy
authors.forename: Julie-Anne
authors.initials: JA
authors.lastname: Fritz
authors.forename: Adele L
authors.initials: AL
authors.lastname: Yates
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: Aude M
authors.initials: AM
authors.lastname: Fahrer
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D033481:Chromosomes, Mammalian / Q000235:genetics*; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D016415:Sequence Alignment; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; C108312:condensin complexes; C522548:kleisen beta protein, mouse; D000251:Adenosine Triphosphatases