title: Transcription factor zinc finger and BTB domain 1 is essential for lymphocyte development.
abstract: Absent T lymphocytes were unexpectedly found in homozygotes of a transgenic mouse from an unrelated project. T cell development did not progress beyond double-negative stage 1 thymocytes, resulting in a hypocellular, vestigial thymus. B cells were present, but NK cell number and B cell isotype switching were reduced. Transplantation of wild-type hematopoietic cells corrected the defect, which was traced to a deletion involving five contiguous genes at the transgene insertion site on chromosome 12C3. Complementation using bacterial artificial chromosome transgenesis implicated zinc finger BTB-POZ domain protein 1 (Zbtb1) in the immunodeficiency, confirming its role in T cell development and suggesting involvement in B and NK cell differentiation. Targeted disruption of Zbtb1 recapitulated the T(-)B(+)NK(-) SCID phenotype of the original transgenic animal. Knockouts for Zbtb1 had expanded populations of bone marrow hematopoietic stem cells and also multipotent and early lymphoid lineages, suggesting a differentiation bottleneck for common lymphoid progenitors. Expression of mRNA encoding Zbtb1, a predicted transcription repressor, was greatest in hematopoietic stem cells, thymocytes, and pre-B cells, highlighting its essential role in lymphoid development.
authors: Department of Pediatrics, University of California San Francisco, San Francisco, CA 91413, USA.
authors: Divya
authors: D
authors: Punwani
authors: Karen
authors: K
authors: Simon
authors: Youngnim
authors: Y
authors: Choi
authors: Amalia
authors: A
authors: Dutra
authors: Diana
authors: D
authors: Gonzalez-Espinosa
authors: Evgenia
authors: E
authors: Pak
authors: Martin
authors: M
authors: Naradikian
authors: Chang-Hwa
authors: CH
authors: Song
authors: Jenny
authors: J
authors: Zhang
authors: David M
authors: DM
authors: Bodine
authors: Jennifer M
authors: JM
authors: Puck
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016335:Zinc Fingers / Q000276:immunology*
chemical_list: D012333:RNA, Messenger; D012097:Repressor Proteins; C570228:ZBTB1 protein, human; C571129:ZBTB1 protein, mouse