Disruption of the mouse Hoxb3 locus affects ventral body wall development

Abstract

Studies of mutant mouse models have revealed that several 30 Hoxb genes play important roles in patterning the axial skeletal structures. Disruption of Hoxb2 and Hoxb4 caused sternal abnormalities and failure in body wall closure, respectively. To better understand the functional roles of the Hoxb3, we have generated mutant mice with insertion of a lacZ reporter in-frame in the Hoxb3 locus, followed by a neomycin resistance cassette. The Hoxb3LacZ heterozygous mutants appeared normal but most of the homozygous mutants died in utero at around 15.5 dpc with severe ventral body wall defects. It has been suggested that the abnormal body wall development may be caused by a combined effect of affecting several neighbouring Hoxb genes, we are currently investigating the expression of Hoxb2 and Hoxb4 in the Hoxb3LacZ homozygous mutants. Analysis of 12.5 dpc embryos revealed defective primary body wall, particularly in the ventral mid-line, in the Hoxb3LacZ homozygous mutant. Skeletal preparation and immunohistochemical analysis of the homozygous mutants at 15.5 dpc indicated normal formation and differentiation of secondary body wall components. However, they all failed to complete their development towards the ventral mid-line, leaving the body covered only by a thin layer of primary wall structure. Further analysis of the homozygous embryos suggested that expression of TGFb2 was reduced in the primary body wall epithelium in early embryos. Our results suggest that deficiency of TGFb2 in the Hoxb3LacZ homozygous mutant may be responsible for the open wall defects, the involvement of TGFb2 related signalling molecules in body wall closure will be investigated.