In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 94, No. 2 ( 1997-01-21), p. 610-615
Abstract:
Bruton tyrosine kinase (Btk) is essential for the development of pre-B cells to mature B cell stages. Btk -deficient mice manifest an X-linked immunodeficiency ( xid ) defect characterized by a reduction of peripheral IgM low IgD high B cells, a lack of peritoneal CD5 + B cells, low serum levels of IgM and IgG3, and impaired responses to T cell independent type II (TI-II) antigens. We have generated transgenic mice in which expression of the human Btk gene is driven by the murine class II major histocompatibility complex Ea gene locus control region, which provides gene expression from the pre-B cell stage onwards. When these transgenic mice were mated onto a Btk − background, correction of the xid B cell defects was observed: B cells differentiated to mature IgM low IgD high stages, peritoneal CD5 + B cells were present, and serum Ig levels and in vivo responses to TI-II antigens were in the normal ranges. A comparable rescue by transgenic Btk expression was also observed in heterozygous Btk +/− female mice in those B-lineage cells that were Btk -deficient as a result of X chromosome inactivation. These findings indicate that the Btk − phenotype in the mouse can be corrected by expression of human Btk from the pre-B cell stage onwards.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.94.2.610
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1997
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
Permalink