Genetics. Published Articles Ahead of Print: October 3, 2005, Copyright © 2005
doi:10.1534/genetics.105.048934


A more recent version of this article appeared on January 1, 2006.

REGULAR RESEARCH PAPERS

A novel murine gene, Sickle tail (Skt), linked to the Danforth's short tail (Sd) locus, is required for normal development of the intervertebral disc

Kei Semba 1, Kimi Araki 1, Zhengzhe Li 1, Ken-ichirou Matsumoto 1, Misao Suzuki 2, Naoki Nakagata 2, Katsumasa Takagi 3, Motohiro Takeya 4, Kumiko Yoshinobu 2, Masatake Araki 2, Kenji Imai 5, Kuniya Abe 6 and Ken-ichi Yamamura 1*

1 Institute of Molecular Embryology and Genetics, Kumamoto University
2 Institute of Resource Development and Analysis, Kumamoto University
3 Department of Orthopaedics Surgery, Kumamoto University School of Medicine
4 Department of Cell Pathology, Kumamoto University School of Medicine
5 GSF-National Research Center for Environment and Hearth
6 BioResource Center, RIKEN

* To whom correspondence should be addressed. E-mail: yamamura{at}gpo.kumamoto-u.ac.jp.

Submitted on July 29, 2005
Revised on September 26, 2005
Accepted on 26 September 2005


Abstract

We established the mutant mouse line, B6;CB-SktGtAyu8021IMEG (SktGt), 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 SktGt/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 +/+ SktGt] and [Sd SktGt/+ +] compound heterozygotes was less than that of Sd heterozygotes. Furthermore, the enhancer trap locus Etl4lacZ, which was previously reported to be an allele of Sd, was located in the third intron of the Skt gene.

Key Words: Danforth's short tail, Etl4lac, Sickle tail gene, notochord, nucleus pulposus