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PMID: 12522149 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Impaired B cell development and function in mice with a targeted disruption of the homeobox gene Hex.

Bogue CW, Zhang PX, McGrath J, Jacobs HC, Fuleihan RL

Abstract

Hex is a homeobox gene that is expressed in all stages of B cell development except plasma cells. We studied lymphocyte development in the absence of Hex by using the RAG1-deficient blastocyst complementation system because homozygous disruption of Hex is embryonic lethal. Hex(-/-);RAG1(-/-) chimeric mice had severely reduced numbers of mature B cells, pre-B cells, and CD5(+) B cells with a striking 15-fold increase in the percentage of B220(-)CD19(+) cells in the bone marrow. Hex(-/-);RAG1(-/-) chimeric mice failed to generate IgG antibodies to T cell-independent antigens, although their serum IgM levels and antibody responses to T cell-dependent antigens were intact. Therefore, Hex is necessary for B cell development and function and its absence results in a dramatic increase in B220(-)CD19(+) cells.

MeSH Terms
Animals Antigens, CD19/analysis B-Lymphocytes/physiology Genes, Homeobox/physiology Homeodomain Proteins/genetics,physiology Immunoglobulin G/biosynthesis Immunoglobulin M/biosynthesis Leukocyte Common Antigens/analysis Lymphopoiesis Mice Mice, Inbred C57BL Transcription Factors
Chemicals
Antigens, CD19 Hhex protein, mouse Homeodomain Proteins Immunoglobulin G Immunoglobulin M Transcription Factors RAG-1 protein Leukocyte Common Antigens
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bogue Clifford W
Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06519, USA. clifford.bogue@yale.edu
Zhang Ping-Xia
McGrath James
Jacobs Harris C
Fuleihan Ramsay L
References (21)
21 references, click to expand
  1. Activation of Hex and mEg5 by retroviral insertion may contribute to mouse B-cell leukemia.
    Oncogene. 1999 Nov 11;18(47):6531-9 PMID: 10597256
  2. Genomic structure, cDNA mapping, and chromosomal localization of the mouse homeobox gene, Hex.
    Mamm Genome. 1999 Oct;10(10):1023-5 PMID: 10501975
  3. Hhex and scl function in parallel to regulate early endothelial and blood differentiation in zebrafish.
    Development. 2000 Oct;127(20):4303-13 PMID: 11003831
  4. Homeobox gene Hex is essential for onset of mouse embryonic liver development and differentiation of the monocyte lineage.
    Biochem Biophys Res Commun. 2000 Oct 5;276(3):1155-61 PMID: 11027604
  5. B cell development pathways.
    Annu Rev Immunol. 2001;19:595-621 PMID: 11244048
  6. Bipotential B-macrophage progenitors are present in adult bone marrow.
    Nat Immunol. 2001 Jan;2(1):83-8 PMID: 11135583
  7. RAG-1-deficient mice have no mature B and T lymphocytes.
    Cell. 1992 Mar 6;68(5):869-77 PMID: 1547488
  8. Identification of a novel vertebrate homeobox gene expressed in haematopoietic cells.
    Nucleic Acids Res. 1992 Nov 11;20(21):5661-7 PMID: 1360645
  9. HEX: a novel homeobox gene expressed during haematopoiesis and conserved between mouse and human.
    Nucleic Acids Res. 1993 Mar 11;21(5):1245-9 PMID: 8096636
  10. RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development.
    Proc Natl Acad Sci U S A. 1993 May 15;90(10):4528-32 PMID: 8506294
  11. PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells.
    Biochem Biophys Res Commun. 1993 Sep 15;195(2):976-83 PMID: 8103988
  12. The Ikaros gene is required for the development of all lymphoid lineages.
    Cell. 1994 Oct 7;79(1):143-56 PMID: 7923373
  13. The helix-loop-helix gene E2A is required for B cell formation.
    Cell. 1994 Dec 2;79(5):875-84 PMID: 8001124
  14. E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements.
    Cell. 1994 Dec 2;79(5):885-92 PMID: 8001125
  15. Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP.
    Cell. 1994 Dec 2;79(5):901-12 PMID: 8001127
  16. Differential expression of a novel proline-rich homeobox gene (Prh) in human hematolymphopoietic cells.
    Blood. 1995 Mar 1;85(5):1237-45 PMID: 7858254
  17. Defective B cell development and function in Btk-deficient mice.
    Immunity. 1995 Sep;3(3):283-99 PMID: 7552994
  18. Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha.
    Science. 1999 Jan 15;283(5400):393-7 PMID: 9888855
  19. Independent regulation of the two Pax5 alleles during B-cell development.
    Nat Genet. 1999 Apr;21(4):390-5 PMID: 10192389
  20. Monoallelic expression of Pax5: a paradigm for the haploinsufficiency of mammalian Pax genes?
    Biol Chem. 1999 Jun;380(6):601-11 PMID: 10430025
  21. The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation.
    Development. 2000 Jun;127(11):2433-45 PMID: 10804184
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2003-01-21
Epub
2003-00-08
Pages
556-61
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC141034
Subset
IM
Grants
NHLBI NIH HHS · K08 HL 03471 · United States
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