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Mice bearing a targeted interruption of the homeobox gene HOXA9 have
defects in myeloid, erythroid, and lymphoid hematopoiesis
HJ Lawrence, CD Helgason, G Sauvageau, S Fong, DJ Izon, RK Humphries and C Largman
Department of Medicine, University of California, San Francisco 94121, USA.
Several homeobox genes of the HOXA and HOXB clusters are expressed in
primitive blood cells, suggesting a role for HOX genes in normal
hematopoiesis. The HOXA9 gene is expressed in CD34+ marrow cells and in
developing lymphocytes. We examined blood-forming organs of mice homozygous
for an interrupted HOXA9 allele to determine if loss of HOX gene function
is deleterious to hematopoiesis. HOXA9-/- mice have approximately 30% to
40% reductions in total leukocytes and lymphocytes (P < .001) and a
blunted granulocytic response to granulocyte colony- stimulating factor
(G-CSF). Homozygous mice have significantly smaller spleens and thymuses.
Myeloid/erythroid and pre-B progenitors in the marrow are significantly
reduced, but no significant decreases are noted in mixed colonies, day 12
colony-forming units-spleen (CFU-S), or long-term culture-initiating cells
(LTC-IC), suggesting little or no perturbation in earlier progenitors.
Heterozygous animals display no hematopoietic defects. The abnormalities in
leukocyte production are transplantable, indicating that the defect resides
in the hematopoietic cells. These studies demonstrate a physiologic role
for a HOX gene in blood cell differentiation, with the greatest apparent
influence of HOXA9 at the level of the committed progenitor.
Volume 89,
Issue 6,
pp. 1922-1930,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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