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

Abstract

Early work on the mouse t-complex was well reviewed by Gruneberg (1943), then reader in genetics at University College, London. The Brachyury or T-locus was discovered by Dobrovolskaia-Zavadskaia in Paris in 1927. Animals heterozygous for T, T/+, have a short tail and homozygotes, T/T, die prenatally. In 1932, however, Dobrovolskaia-Zavadskaia reported on three lines of tailless mice which had been obtained by crossing T/+ animals with mice derived from the wild (Dobrovolskaia-Zavadskaia, 1927). Each of the tailless lines bred true, and in 1935 it was suggested that each line constituted a balanced lethal system in which T/t animals were tailless and both T/T and t/t died prenatally. Later, two of the three lines were proved to carry the same recessive lethal, called t0, and the other a different lethal, called t1. Genetically t0/t1 animals were viable and normal-tailed. However, t0/t1 males were sterile. In early breeding studies, T/t0 and T/t1 females transmitted T and t normally in equal ratios to their offspring. However, both T/t0 and T/t1 males gave a large excess of young carrying t0 or t1 over the expected Mendelian value of 50%. The abnormal ratios were not due to misclassification of T and t, nor to reduced viability of Tcarrying young. Thus, T/t males transmit the t-allele with an abnormally high ratio. Reviewing the work at this stage, Gruneberg made the prescient suggestion that the properties of t-alleles (as they were then known) could be due to inversions or to other structural changes. Further properties of the t-complex were discovered soon after. Dunn and Caspari found crossover-suppression between T and the nearby locus of Fu in mice heterozygous for t (Dunn and Caspari, 1945), and in balanced lethal T/t stocks Dunn found repeat "mutations" to other t’s (Dunn and Gluecksohn-Schoenheimer, 1950), either lacking lethality or with a new complementing lethal. t-alleles were found commonly in wild mouse populations. Most naturally occurring t’s were recessive lethals but some were viable when homozygous; however, homozygous males were sterile. Dunn and his co-workers suggested that t’s were maintained in the wild by their high transmission from heterozygous males.