RRC ID 43255
著者 Pérez de Diego R, López-Granados E, Rivera J, Ferreira A, Fontán G, Bravo J, García Rodríguez MC, Bolland S.
タイトル Naturally occurring Bruton's tyrosine kinase mutations have no dominant negative effect in an X-linked agammaglobulinaemia cellular model.
ジャーナル Clin Exp Immunol
Abstract X-linked agammaglobulinaemia (XLA) is characterized by absence of mature B cells because of mutations in the Bruton's tyrosine kinase (Btk) gene. Btk-deficient early B cell precursors experience a block in their differentiation potentially reversible by the addition of an intact Btk gene. Btk expression was measured in 69 XLA patients with 47 different mutations and normal expression was detected in seven. We characterized these Btk mutant forms functionally by transfection into a lymphoma cell line that lacks endogenous Btk expression (Btk-/- DT40 cells) and analysed the calcium flux in response to B cell receptor stimulation. To test whether co-expression of a mutated form could compromise the function of the intact Btk transfection, studies in wild-type (WT) DT40 cells were also performed. Study reveals that none of the seven Btk mutants analysed was able to revert the absence of calcium mobilization upon IgM engagement in Btk-/- DT40 cells, as does intact Btk. In addition, calcium mobilization by anti-IgM stimulation in DT40 Btk+/+ cells was unaffected by co-expression with Btk mutants. These results suggest that gene addition would be feasible not only for patients with XLA and mutations that prevent Btk expression, but for those with expression of a mutant Btk.
巻・号 152(1)
ページ 33-8
公開日 2008-4-1
DOI 10.1111/j.1365-2249.2008.03589.x
PII CEI3589
PMID 18241233
PMC PMC2384054
MeSH Agammaglobulinaemia Tyrosine Kinase Agammaglobulinemia / genetics* Agammaglobulinemia / metabolism Animals Calcium / metabolism Chickens Child Child, Preschool Genetic Diseases, X-Linked / genetics* Genetic Diseases, X-Linked / metabolism Humans Immunoglobulin M / immunology Infant Male Mutagenesis, Site-Directed Mutation* Mutation, Missense Protein-Tyrosine Kinases / genetics* Protein-Tyrosine Kinases / metabolism Transfection Tumor Cells, Cultured
IF 3.532
引用数 4
リソース情報
ヒト・動物細胞