A UK-centric history of studies on the mouse t-complex

Abstract

The t-complex of the mouse was discovered over 70 years' ago and British geneticists have been involved in studies on this fascinating region of the mouse genome for 50 years. As a classical genetic system, t-complex studies have illuminated the nature of inversion polymorphism and recombination suppression, the behaviour of non-Mendelian factors and transmission ratio distortion, and genetic imprinting. This work helped to establish the t- complex region on chromosome 17 as one of the best mapped and characterised mouse chromosomes, and provided the framework for pioneering positional cloning and genome analysis approaches. Brachyury, T, was the first mouse gene isolated by positional cloning and this was a direct consequence of the genetic and structural analysis of the t-complex. Tcp-1 was discovered and subsequently molecularly cloned by the application of novel 2D-PAGE technology and differential cDNA cloning in conjunction with genetic analysis of partial t-haplotypes. Characterisation of the DNA- binding transcription factor T has been a vital and unique contribution to vertebrate developmental genetics. TCP-1 is a component of the chaperonin containing TCP-1, CCT, an absolutely conserved protein folding machine present in the cytosol of all eukaryotes. We look forward to the complete DNA sequencing of the 30MBp t- complex within the next few years. Then perhaps the major outstanding problem of the components and mechanism of male transmission ratio distortion will be elucidated.