Genetical Studies on the Skeleton of the Mouse1 : XXII. The Development of Danforth’s Short-tail

Abstract

An embryological investigation of the semi-dominant gene for Danforth’s short-tail in the mouse shows that, contrary to the results of earlier investigations, the syndrome can be understood as a unitary system dependent on a single root cause. The effects of the gene are similar in heterozygotes and homozygotes, but more extreme in the latter. The most fundamental anomaly probably resides in the primitive streak. This gives rise to a structurally abnormal notochord with a reduced calibre. The abnormality of the notochord increases in intensity in a cranio-caudal direction. At a somewhat later stage the notochord disintegrates all along its length. The process starts in the cervical region where it is also most complete. As a direct result of the disintegration of the notochord there is a reduction of the nuclei pulposi of the intervertebral disks and a reduction of the centra of the vertebrae, particularly in the cervical region; the dens epistrophei is virtually absent, and as a result of this anomaly, an atypical but fully functional horse-shoe articulation is formed between the first two cervical vertebrae with yet more remote effects on neighbouring muscles. The abnormality of the notochord is responsible for regressive processes (cell pyknosis) which at a later stage lead to the loss of part or the whole of the tail. The abnormality of the notochord is also responsible for a considerable reduction of the cloaca and the tail-gut. The cloaca is too small for the development of a urorectal septum and hence persists; the shrinkage of the cloaca also leads to a (? secondary) separation from the cloacal membrane; this results in absence of the bladder, urethra, and genital papilla. Finally, there is an arrest or delay in the establishment of contact between the reduced cloaca and the Wolffian ducts; it is suggested that this may interfere with the growth of the ureter buds and thus, in turn, lead to the absence of the metanephros. Further minor effects of the Sd gene include right-to-left connexions between paraxial mesoderm or somites in the tail, a slight effect on the ventral ectodermal ridge of the tail, and a statistical effect on the metoptic roots of the ala orbitalis of the presphenoid. All these effects are clearly secondary, but the mechanism of the last two of them is not understood in detail.