Disruption of the homeobox gene Hoxb-6 in mice results in increased numbers of early erythrocyte progenitors

Abstract

Hox genes encode transcription factors that are required for proper development of certain tissues and for patterning of the hindbrain, the limbs, and skeleton. They are also expressed in the hematopoietic system with a preference for specific cell lineages. To determine the role of Hoxb-6 in normal hematopoiesis, mice with a targeted disruption in the Hoxb-6 gene were generated. Mature hematopoietic cell types and immune responses are normal in homozygous Hoxb-6 mutants. Clonogenic progenitor cell assays demonstrate an increased number of early erythroid progenitor cells in the bone marrow and fetal liver of mutants, while differentiation of other cell lineages is unaffected. These results suggest that Hoxb-6 controls the generation, proliferation, or survival of erythroid progenitor cells. Am.

Folate modulates Hox gene‐controlled skeletal phenotypes

“…Mice with a targeted disruption of the Hoxb6 gene (Kappen, 2000) exhibit homeotic transformations of vertebra at the cervico-thoracic junction, encompassing incomplete development of the first pair of ribs (Kappen, manuscript submitted). Most notably, the rib heads are defective and do not articulate properly with the vertebral body.…”

“…This indicates that overexpression of Hoxd4, and according to the cell culture evidence Hoxc8 (Cormier et al, 2003), induces reversible changes in chondrocytes rather than re-programming a cellular differentiation pathway. Prior work on the role of Hox genes in skeletal patterning (Condie and Capecchi, 1993;Kessel, 1992;Knezevic et al, 1997;Yokouchi et al, 1995) and in the hematopoietic system (Kappen, 2000;Lawrence et al, 1997;Perkins et al, 1990;Sauvageau et al, 1997;Shen et al, 1992) predicted that tissue-specific alterations in Hox gene expression lead to irreversible changes in cell fate and differentiation. Instead, the reversibility of cartilage defects in our Hoxd4 transgenic mice clearly indicates that Hoxd4 overexpression does not affect cell fate determination.…”

Hox genes in hematopoiesis and leukemogenesis

“…Additional Hox knockout models where hematopoiesis was assessed include Hoxa5 (Fuller et al, 1999), Hoxa7 (So et al, 2004), Hoxa10 (Lawrence et al, 2005), Hoxb3 (Ko et al, 2007), Hoxb6 (Shen et al, 1992;Kappen, 2000) and Hoxc8 (Shimamoto et al, 1999) ( Figure 1). In summary, their effects range from impaired HSC selfrenewal to impaired myelopoiesis or B lymphopoiesis.…”

De novo t(12;17)(p13.3;q21.3) translocation with a breakpoint near the 5′ end of the HOXB gene cluster in a patient with developmental delay and skeletal malformations

“…32 Hoxb6 controls generation, proliferation, and/or survival of erythroid progenitor cells. 33 Hoxb7 knockout mice have fused ribs in the upper thoracic region. 34 Hoxb8 knockouts show abnormal grooming behavior and central nervous system abnormalities, 35 whereas ectopic expression of Hoxb8 results in a mirrorimage duplication in the forelimb.…”