Developmental and functional impairment of T cells in mice lacking CD3 zeta chains.
CD3 zeta is a component of the T cell antigen receptor (TCR) complex and is important for signal transduction. We have established mice selectively lacking CD3 zeta but able to express CD3 eta, a polypeptide produced from the same locus through alternative splicing, using the method of gene targeting in embryonic stem cells. In homozygous mutant mice, the numbers of thymocytes and peripheral T cells were greatly reduced and the expression levels of TCR on these cells were 5-fold lower than those on wild-type cells. By contrast, TCR gamma delta+ intestinal intraepithelial lymphocytes were not obviously affected by the mutation. T cells from homozygous mutants exhibited an impaired proliferative response. These results imply that CD3 zeta has a critical role in the development and signal transduction of T cells in vivo.
Ohno
H
H
Division of Molecular Genetics, Chiba University, School of Medicine, Japan.
Aoe
T
T
Taki
S
S
Kitamura
D
D
Ishida
Y
Y
Rajewsky
K
K
Saito
T
T
D000818:Animals; D001483:Base Sequence; D001773:Blood Cells / Q000166:cytology / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics*; D006720:Homozygote; D007422:Intestines / Q000166:cytology / Q000196:embryology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D015398:Signal Transduction; D013234:Stem Cells; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology
D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell