title: HAX1 deficiency: impact on lymphopoiesis and B-cell development.
abstract: 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.
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Peckl-Schmid
authors.forename: Susanne
authors.initials: S
authors.lastname: Wolkerstorfer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Königsberger
authors.forename: Gertrude
authors.initials: G
authors.lastname: Achatz-Straussberger
authors.forename: Stefan
authors.initials: S
authors.lastname: Feichtner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schwaiger
authors.forename: Nadja
authors.initials: N
authors.lastname: Zaborsky
authors.forename: Michael
authors.initials: M
authors.lastname: Huemer
authors.forename: Iris K
authors.initials: IK
authors.lastname: Gratz
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.forename: Marinus
authors.initials: M
authors.lastname: Lamers
authors.forename: Reto
authors.initials: R
authors.lastname: Crameri
authors.forename: Katrin
authors.initials: K
authors.lastname: Moser
authors.forename: Elke O
authors.initials: EO
authors.lastname: Luger
authors.forename: Gernot
authors.initials: G
authors.lastname: Achatz
mesh_terms: 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
chemical_list: C514936:CXCR4 protein, mouse; C491295:Hs1bp1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D019718:Receptors, CXCR4; D017493:Leukocyte Common Antigens