HAX1 deficiency: impact on lymphopoiesis and B-cell development.
HAX1 was originally described as HS1-associated protein with a suggested function in receptor-mediated apoptotic and proliferative responses of lymphoid cells. Recent publications refer to a complex and multifunctional role of this protein. To investigate the in vivo function of HAX1 (HS1-associated protein X1) in B cells, we generated a Hax1-deficient mouse strain. Targeted deletion of Hax1 resulted in premature death around the age of 12 wk accompanied by a severe reduction of lymphocytes in spleen, thymus and bone marrow. In the bone marrow, all B-cell populations were lost comparably. In the spleen, B220(+) cells were reduced by almost 70%. However, as investigated by adoptive transfer experiments, this impairment is not exclusively B-cell intrinsic and we hypothesize that a HAX1-deficient environment cannot sufficiently provide the essential factors for proper lymphocyte development, trafficking and survival. Hax1(-/-) B cells show a significantly reduced expression of CXCR4, which might have an influence on the observed defects in B-cell development.
Peckl-Schmid
Doris
D
Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
Wolkerstorfer
Susanne
S
Königsberger
Sebastian
S
Achatz-Straussberger
Gertrude
G
Feichtner
Stefan
S
Schwaiger
Elisabeth
E
Zaborsky
Nadja
N
Huemer
Michael
M
Gratz
Iris K
IK
Schibli
Roger
R
Lamers
Marinus
M
Crameri
Reto
R
Moser
Katrin
K
Luger
Elke O
EO
Achatz
Gernot
G
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
C514936:CXCR4 protein, mouse; C491295:Hs1bp1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D019718:Receptors, CXCR4; D017493:Leukocyte Common Antigens