A mutation in a chromosome condensin II subunit, kleisin beta, specifically disrupts T cell development.
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.
Gosling
Katharine M
KM
School of Biochemistry and Molecular Biology, John Curtin School of Medical Research, and Australian Phenomics Facility, Australian National University, Canberra ACT 0200, Australia.
Makaroff
Lydia E
LE
Theodoratos
Angelo
A
Kim
Yong-Hee
YH
Whittle
Belinda
B
Rui
Lixin
L
Wu
Hua
H
Hong
Nancy A
NA
Kennedy
Gavin C
GC
Fritz
Julie-Anne
JA
Yates
Adele L
AL
Goodnow
Christopher C
CC
Fahrer
Aude M
AM
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*
D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; C108312:condensin complexes; C522548:kleisen beta protein, mouse; D000251:Adenosine Triphosphatases