HAX1 deficiency: Impact on lymphopoiesis and B-cell development

✍ Scribed by Doris Peckl-Schmid; Susanne Wolkerstorfer; Sebastian Königsberger; Gertrude Achatz-Straussberger; Stefan Feichtner; Elisabeth Schwaiger; Nadja Zaborsky; Michael Huemer; Iris K. Gratz; Roger Schibli; Marinus Lamers; Reto Crameri; Katrin Moser; Elke O Luger; Gernot Achatz

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 633 KB
• Volume: 40
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200940221

✦ Synopsis

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.