A Novel Murine Gene, Sickle tail, Linked to the Danforth's short tail Locus, Is Required for Normal Development of the Intervertebral Disc

Author:

Semba Kei12,Araki Kimi1,Li Zhengzhe1,Matsumoto Ken-ichirou12,Suzuki Misao3,Nakagata Naoki4,Takagi Katsumasa2,Takeya Motohiro5,Yoshinobu Kumiko6,Araki Masatake6,Imai Kenji7,Abe Kuniya8,Yamamura Ken-ichi1

Affiliation:

1. Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 862-0976, Japan

2. Department of Orthopaedic Surgery, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan

3. Division of Transgenic Technology, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan

4. Division of Reproductive Engineering, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan

5. Department of Cell Pathology, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan

6. Division of Bioinformatics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan

7. Institute of Developmental Genetics, GSF-National Research Center for Environment and Health, 85764 Neuherberg, Germany and

8. Technology Development Team for Mammalian Cellular Dynamics, BioResource Center, RIKEN, Tsukuba, Ibaraki 305-0074 Japan

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Genetics

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