Scientific Article
previous document  unige:11516  next document
add to browser collection
Title

A Btk transgene restores the antiviral TI-2 antibody responses of xid mice in a dose-dependent fashion

Authors
Ochsenbein, A. F.
Satterthwaite, A. B.
Witte, O. N.
Hengartner, Hans
Zinkernagel, R. M.
Published in European Journal of Immunology. 1999, vol. 29, no. 9, p. 2981-2987
Abstract X-linked agammaglobulinemia in humans and X-linked immunodeficiency (xid) in mice are both caused by mutations in Bruton's tyrosine kinase (Btk). Xid mice lack the early T cell-independent type 2 (TI-2) antibody response to polio virus and to a recombinant vaccinia virus (Vacc-IND-G) expressing the neutralizing determinant of vesicular stomatitis virus (VSV). This response could be restored by introduction of one or two copies of a murine Btk cDNA transgene driven by the Ig heavy chain promoter plus enhancer and depended crucially on a sufficient Btk expression level. Introduction of the same transgene into wild-type mice had little to no negative effect. The TI-1 antibody response to VSV and the T cell-dependent response to lymphocytic choriomeningitis virus were comparable in all mice tested. All mice analyzed eventually reached similar primary and memory antibody titers against all viruses independent of the mouse Btk genotype. These studies show that the xid mutation in mice has no dominant negative effect and that a transgene - even when not provided in the natural genetic context - may be able to restore functional defects resulting from genetic mutation.
Keywords AnimalsAntibodies, Viral/ biosynthesis/immunologyAntigens, Viral/immunologyCommon Variable Immunodeficiency/genetics/immunologyDNA, Viral/genetics/immunologyDose-Response Relationship, ImmunologicMiceMice, Inbred BALB CMice, Inbred C3HMice, Inbred C57BLMice, TransgenicProtein-Tyrosine Kinases/ genetics/ immunology/metabolismT-Lymphocytes/ immunology/virologyTransgenes/ immunology
Identifiers
PMID: 10508272
Full text
Citation
(ISO format)
PINSCHEWER, Daniel et al. A Btk transgene restores the antiviral TI-2 antibody responses of xid mice in a dose-dependent fashion. In: European Journal of Immunology, 1999, vol. 29, n° 9, p. 2981-2987. https://archive-ouverte.unige.ch/unige:11516

177 hits

0 download

Update

Deposited on : 2010-08-27

Export document
Format :
Citation style :