Document Detail


Inactivation of Btk by insertion of lacZ reveals defects in B cell development only past the pre-B cell stage.
MedLine Citation:
PMID:  8890160     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bruton's tyrosine kinase (Btk) is a cytoplasmic protein kinase that is defective in X-linked agammaglobulinaemia in man and in X-linked immunodeficiency in the mouse. There is controversy regarding the stages of B cell development that are dependent on Btk function. To determine the point in B cell differentiation at which defects in Btk become apparent, we generated a mouse model by inactivating the Btk gene through an in-frame insertion of a lacZ reporter by homologous recombination in embryonic stem cells. The phenomenon of X-chromosome inactivation in Btk+/- heterozygous female mice enabled us to evaluate the competition between B cell progenitors expressing wild-type Btk and those expressing the Btk-/lacZ allele in each successive step of development. Although Btk was already expressed in pro-B cells, the first selective disadvantage only became apparent at the transition from small pre-B cells to immature B cells in the bone marrow. A second differentiation arrest was found during the maturation from IgD(low)IgM(high) to IgD(high)IgM(low) stages in the periphery. Our results show that Btk expression is essential at two distinct differentiation steps, both past the pre-B cell stage.
Authors:
R W Hendriks; M F de Bruijn; A Maas; G M Dingjan; A Karis; F Grosveld
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The EMBO journal     Volume:  15     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  1996 Sep 
Date Detail:
Created Date:  1996-12-10     Completed Date:  1996-12-10     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  4862-72     Citation Subset:  IM    
Affiliation:
Department of Cell Biology and Genetics, Faculty of Medicine, Erasmus University Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Agammaglobulinemia / genetics
Alleles
Animals
B-Lymphocytes / cytology*
Blotting, Western
Cell Differentiation
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Genes, Reporter
Hematopoietic Stem Cells / cytology
Immunoglobulin D / analysis
Immunoglobulin M / analysis
Lac Operon*
Male
Mice
Phenotype
Plasmids / metabolism
Protein-Tyrosine Kinases / genetics*,  physiology
Transfection
Chemical
Reg. No./Substance:
0/Immunoglobulin D; 0/Immunoglobulin M; EC 2.7.10.1/Agammaglobulinaemia tyrosine kinase; EC 2.7.10.1/Protein-Tyrosine Kinases
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