IS THERE A BRACHYURY THE 2ND - ANALYSIS OF A TRANSGENIC MUTATION INVOLVED IN NOTOCHORD MAINTENANCE IN MICE

A new phenotype mapping to the t-complex, which is designated Brachyur y the Second (T2), is characterized by a slightly shortened tail in he terozygotes and homozygous failure to form an organized notochord with subsequent abnormal development of posterior somites and neural tube. The phenotype of T2 superficially resembles that of Brachyury; howeve r, there are several. important differences. Brachyury homozygotes fai l to make posterior somites, notochord, floor plate, and a placental c onnection, resulting in death by 10.5 days of development. In contrast , T2 homozygotes make posterior somites, scattered notochord cells, an d floorplate and achieve an allantoic connection. However, despite mak ing a maternal connection, T2 homozygotes cease development at E11.5 a nd die soon after. We have cloned and analyzed the transgene insertion site, which maps within 100 kb of the Brachyury gene, but does not se em to physically interrupt nor affect transcription from that locus. T he existence of a second gene mapping near Brachyury and affecting the same developmental processes was alluded to over 50 years ago and has been debated ever since. An embryological description of T2 is presen ted, as is a discussion of the implications of a single, larger Brachy ury locus versus two closely linked genes coordinately regulating axia l development. (C) 1995 Academic Press, Inc.