A novel murine gene, Sickle tail, linked to the Danforth's short tail locus, is required for normal development of the intervertebral disc.
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.
Semba
Kei
K
Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 862-0976, Japan.
Araki
Kimi
K
Li
Zhengzhe
Z
Matsumoto
Ken-ichirou
K
Suzuki
Misao
M
Nakagata
Naoki
N
Takagi
Katsumasa
K
Takeya
Motohiro
M
Yoshinobu
Kumiko
K
Araki
Masatake
M
Imai
Kenji
K
Abe
Kuniya
K
Yamamura
Ken-ichi
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000235:genetics; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D005091:Exons / Q000235:genetics; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D007403:Intervertebral Disc / Q000002:abnormalities*; D008297:Male; D051379:Mice / Q000196:embryology / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D009672:Notochord / Q000002:abnormalities / Q000196:embryology; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism; D013623:Tail / Q000002:abnormalities* / Q000196:embryology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D011506:Proteins; D001616:beta-Galactosidase