Mouse mutant "rib-vertebrae" (rv): a defect in somite polarity

The recessive mouse mutant rib-vertebrae (rv) affects the morphogenesis of the axial skeleton. The phenotype is characterized by vertebral defects such as fusion of adjacent segments, hemivertebrae, or open neural arches and rib defects including fusions, forked ribs, and additional ribs. We have analyzed this mutant in detail and are able to show that defective somite patterning underlies the vertebral malformations. The rv mutation leads to an elongation of the presomitic mesoderm and a disruption of the anterior-posterior polarization of somites, as indicated by the abnormal expression of Pax1 and Mox1. Somites are irregular in size but the overall formation of somites appears unaffected. These changes are reminiscent of somite defects obtained in loss of function alleles of the Delta-Notch pathway. Expression of the Notch pathway components Delta-like-1 (Dll1) and lunatic fringe (Lfng) are altered in rv mutants. To investigate possible interactions of rv with components of the Notch pathway, we crossed rv into Dll1(lacZ). Double heterozygous (rv/+; Dll1(lacZ)/+) mice show vertebral defects and homozygous animals with one inactive Dll1 allele (rv/rv; Dll1(lacZ)/+) exhibit a dramatic increase in phenotypic severity, indicating that rv and Dll1 genetically interact. We have mapped rv to a region on chromosome 7 that is syntenic to human chromosomes 11p, 10q, and 11p. rv is phenotypically similar to human vertebral malformations syndromes and can serve as a model for these conditions.