The mouse rib-vertebrae mutation is a hypomorphic Tbx6 allele

Rib-vertebrae (rv) is an autosomal recessive mutation in mouse that affects somite formation, morphology, and patterning. Expression of Notch pathway components is affected in the paraxial mesoderm of rv mutant embryos, and rv and a null allele of the Notch ligand delta1 show non-allelic non-complementation. By fine genetic mapping and complementation testing we have identified Tbx6, a gene essential for paraxial mesoderm formation, as the gene mutated in rv. Compound heterozygotes carrying a Tbx6 null allele and rv show a phenotype that is milder than in homozygous Tbx6 null but more severe than in homozygous rv mutants. Tbx6 expression is down-regulated in rv mutant embryos. An insertion in the promoter region upstream of the transcriptional start is present in the genome of rv mutants but not in different strains of mice wild type for Tbx6. Our results indicate that rv is a regulatory mutation of Tbx6 causing a hypomorphic phenotype.