Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice.
The T cell protein tyrosine phosphatase (TC-PTP) is one of the most abundant mammalian tyrosine phosphatases in hematopoietic cells; however, its role in hematopoietic cell function remains unknown. In this report, we investigated the physiological function(s) of TC-PTP by generating TC-PTP-deficient mutant mice. The three genotypes (+/+, +/-, -/-) showed mendelian segregation at birth (1:2:1) demonstrating that the absence of TC-PTP was not lethal in utero, but all homozygous mutant mice died by 3-5 wk of age, displaying runting, splenomegaly, and lymphadenopathy. Homozygous mice exhibited specific defects in bone marrow (BM), B cell lymphopoiesis, and erythropoiesis, as well as impaired T and B cell functions. However, myeloid and macrophage development in the BM and T cell development in the thymus were not significantly affected. BM transplantation experiments showed that hematopoietic failure in TC-PTP -/- animals was not due to a stem cell defect, but rather to a stromal cell deficiency. This study demonstrates that TC-PTP plays a significant role in both hematopoiesis and immune function.
You-Ten
K E
KE
Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Muise
E S
ES
Itié
A
A
Michaliszyn
E
E
Wagner
J
J
Jothy
S
S
Lapp
W S
WS
Tremblay
M L
ML
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology / Q000502:physiology*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002455:Cell Division; D005720:Gamma Rays; D018390:Gene Targeting; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006720:Homozygote; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014916:Whole-Body Irradiation
D015703:Antigens, CD; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D017027:Protein Tyrosine Phosphatases; C516653:Ptpn2 protein, mouse