We established the mutant mouse line, B6;CB-Skt GtAyu8021IMEG (Skt Gt ), through gene-trap mutagenesis in embryonic stem cells. The novel gene identified, called Sickle tail (Skt), is composed of 19 exons and encodes a protein of 1352 amino acids. Expression of a reporter gene was detected in the notochord during embryogenesis and in the nucleus pulposus of mice. Compression of some of the nuclei pulposi in the intervertebral discs (IVDs) appeared at embryonic day (E) 17.5, resulting in a kinky-tail phenotype showing defects in the nucleus pulposus and annulus fibrosus of IVDs in Skt Gt/Gt mice. These phenotypes were different from those in Danforth's short tail (Sd) mice in which the nucleus pulposus was totally absent and replaced by peripheral fibers similar to those seen in the annulus fibrosus in all IVDs. The Skt gene maps to the proximal part of mouse chromosome 2, near the Sd locus. The genetic distance between them was 0.95 cM. The number of vertebrae in both [Sd 1/1 Skt Gt ] and [Sd Skt Gt /1 1] compound heterozygotes was less than that of Sd heterozygotes. Furthermore, the enhancer trap locus Etl4 lacZ , which was previously reported to be an allele of Sd, was located in the third intron of the Skt gene. T HE notochord is an integral component of the axial structure of vertebrates, functions as a signaling center during embryogenesis, and plays essential roles in patterning of both somites and the neural tube (Ang and Rossant 1994; Wilson et al.1995; Chiang et al.1996). In addition, the notochord has major roles in vertebral column formation. In the mouse, the notochord is a continuous rod of constant diameter extending from the hypophysis to almost the tip of the tail at embryonic day (E) 9.5. At E10.5-E11.5, signals from the notochord induce the migration, proliferation, and fusion of the sclerotome to form a continuous and unsegmented perichordal tube around the notochord and neural tube. At 12.5, mesenchyme acquires a characteristic metameric pattern of densely packed areas caudally and loosely packed areas cranially. Some densely packed cells move cranially and give rise to the annulus fibrosus of the future intervertebral disc (IVD). The remaining densely packed cells fuse with the immediately caudal loosely packed cells to form the cartilaginous primordia of the vertebral bodies. Notochord cells located in the vertebral body of cranial regions start to relocate into intervertebral regions (Paavola et al. 1980;Rufai et al. 1995;Aszodi et al. 1998). At E13.5, the vertebral regions are enlarged and chondrified. The notochord proliferates and undergoes hypertrophy to form the gelatinous center of the intervertebral disc, called the nucleus pulposus. This nucleus is surrounded by the circularly arranged fibers of the annulus fibrosus. These two structures together constitute the IVD (Langman 1969;Theiler 1988 intervertebral regions. Failures in somite, neural tube, and notochord formation are closely correlated with vertebral malformations. However, the mechanisms that underlie the formatio...

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