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 Blood, 15 September 2006, Vol. 108, No. 6, pp. 1857-1864.
Prepublished online as a Blood First Edition Paper on May 30, 2006; DOI 10.1182/blood-2005-10-007658.

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HEMATOPOIESIS

Adult murine hematopoiesis can proceed without beta1 and beta7 integrins

Gerd Bungartz, Sebastian Stiller, Martina Bauer, Werner Müller, Angela Schippers, Norbert Wagner, Reinhard Fässler, and Cord Brakebusch

From the Max Planck Institute of Biochemistry, Department of Molecular Medicine, and the Heisenberg Group "Regulation of Cytoskeletal Organization," Martinsried, Germany; the German Research Center for Biotechnology (GBF), Department of Experimental Immunology, Braunschweig, Germany; and the Department of Pediatrics, City Hospital of Dortmund, Germany.

The function of {alpha}4beta1 and {alpha}4beta7 integrins in hematopoiesis is controversial. While some experimental evidence suggests a crucial role for these integrins in retention and expansion of progenitor cells and lymphopoiesis, others report a less important role in hematopoiesis. Using mice with a deletion of the beta1 and the beta7 integrin genes restricted to the hematopoietic system we show here that {alpha}4beta1 and {alpha}4beta7 integrins are not essential for differentiation of lymphocytes or myelocytes. However, beta1beta7 mutant mice displayed a transient increase of colony-forming unit (CFU-C) progenitors in the bone marrow and, after phenylhydrazine-induced anemia, a decreased number of splenic erythroid colony-forming units in culture (CFUe's). Array gene expression analysis of CD4+CD8+ double-positive (DP) and CD4–CD8– double-negative (DN) thymocytes and CD19+ and CD4+ splenocytes did not provide any evidence for a compensatory mechanism explaining the mild phenotype. These data show that {alpha}4beta1 and {alpha}4beta7 are not required for blood cell differentiation, although in their absence alterations in numbers and distribution of progenitor cells were observed.


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