Mutation watch: mouse brachyury (T), the T-box gene family, and human disease.

Abstract

The classical mouse mutation brachyury (‘‘short tail’’), first described in 1927, is located in the T/t region of proximal mouse Chromosome (Chr) 17. Heterozygotes for null alleles of brachyury have short tails and mild skeletal defects due to haploinsufficiency. Homozygous null mice have a severe developmental disorder that includes defective mesoderm formation and regression of the notochord, and they do not survive beyond E10. Seventy years of work on the short tail mouse has resulted in isolation of an important family of transcriptional regulators of early development, as well as the recent identification of the genes responsible for two complex human developmental disorders: the Holt-Oram syndrome of cardiac and limb defects, and the ulnar-mammary syndrome affecting limb, tooth, and genital development.