Abstract
The Wiskott-Aldrich syndrome (WAS) is a human X-linked immunodeficiency resulting from mutations in a gene (WASP) encoding a cytoplasmic protein implicated in regulating the actin cytoskeleton. To elucidate WASP function, we disrupted the WASP gene in mice by gene-targeted mutation. WASP-deficient mice showed apparently normal lymphocyte development, normal serum immunoglobulin levels, and the capacity to respond to both T-dependent and T- indepedent type II antigens. However, these mice did have decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Moreover, purified WASP-deficient T cells showed markedly impaired proliferation and antigen receptor cap formation in response to anti-CD3ε stimulation. Yet, purified WASP-deficient B cells showed normal responses to anti-lg stimulation. We discuss the implications of our findings regarding WASP function in receptor signaling and cytoskeletal reorganization in T and B cells and compare the effects of WASP deficiency in mice and humans.
| Original language | English |
|---|---|
| Pages (from-to) | 81-91 |
| Number of pages | 11 |
| Journal | Immunity |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 1 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
- Immunology
Cite this
Wiskoff-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. / Snapper, Scott B.; Rosen, Fred S.; Mizoguchi, Emiko; Cohen, Paul; Khan, Wasif; Liu, Ching Hui; Hagemann, Tracy L.; Kwan, Sau Ping; Ferrini, Roger; Davidson, Laurie; Bhan, Atul K.; Alt, Frederick W.
In: Immunity, Vol. 9, No. 1, 01.07.1998, p. 81-91.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Wiskoff-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation
AU - Snapper, Scott B.
AU - Rosen, Fred S.
AU - Mizoguchi, Emiko
AU - Cohen, Paul
AU - Khan, Wasif
AU - Liu, Ching Hui
AU - Hagemann, Tracy L.
AU - Kwan, Sau Ping
AU - Ferrini, Roger
AU - Davidson, Laurie
AU - Bhan, Atul K.
AU - Alt, Frederick W.
PY - 1998/7/1
Y1 - 1998/7/1
N2 - The Wiskott-Aldrich syndrome (WAS) is a human X-linked immunodeficiency resulting from mutations in a gene (WASP) encoding a cytoplasmic protein implicated in regulating the actin cytoskeleton. To elucidate WASP function, we disrupted the WASP gene in mice by gene-targeted mutation. WASP-deficient mice showed apparently normal lymphocyte development, normal serum immunoglobulin levels, and the capacity to respond to both T-dependent and T- indepedent type II antigens. However, these mice did have decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Moreover, purified WASP-deficient T cells showed markedly impaired proliferation and antigen receptor cap formation in response to anti-CD3ε stimulation. Yet, purified WASP-deficient B cells showed normal responses to anti-lg stimulation. We discuss the implications of our findings regarding WASP function in receptor signaling and cytoskeletal reorganization in T and B cells and compare the effects of WASP deficiency in mice and humans.
AB - The Wiskott-Aldrich syndrome (WAS) is a human X-linked immunodeficiency resulting from mutations in a gene (WASP) encoding a cytoplasmic protein implicated in regulating the actin cytoskeleton. To elucidate WASP function, we disrupted the WASP gene in mice by gene-targeted mutation. WASP-deficient mice showed apparently normal lymphocyte development, normal serum immunoglobulin levels, and the capacity to respond to both T-dependent and T- indepedent type II antigens. However, these mice did have decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Moreover, purified WASP-deficient T cells showed markedly impaired proliferation and antigen receptor cap formation in response to anti-CD3ε stimulation. Yet, purified WASP-deficient B cells showed normal responses to anti-lg stimulation. We discuss the implications of our findings regarding WASP function in receptor signaling and cytoskeletal reorganization in T and B cells and compare the effects of WASP deficiency in mice and humans.
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UR - http://www.scopus.com/inward/citedby.url?scp=0032118427&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(00)80590-7
DO - 10.1016/S1074-7613(00)80590-7
M3 - Article
C2 - 9697838
AN - SCOPUS:0032118427
VL - 9
SP - 81
EP - 91
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 1
ER -