Ectopic expression of Ptf1a induces spinal defects, urogenital defects, and anorectal malformations in Danforth's short tail mice.

Danforth's short tail (Sd) is a semidominant mutation on mouse chromosome 2, characterized by spinal defects, urogenital defects, and anorectal malformations. However, the gene responsible for the Sd phenotype was unknown. In this study, we identified the molecular basis of the Sd mutation.

A Cre knock-in mouse line on the Sickle tail locus induces recombination in the notochord and intervertebral disks.

Sickle tail (Skt) was originally identified by gene trap mutagenesis in mice, and the trapped gene is highly expressed in the notochord, intervertebral discs (IVD), and mesonephros. Here, we report the generation of Skt(cre) mice expressing Cre recombinase in the IVD due to target insertion of the cre gene into the Skt locus by recombinase-mediated cassette exchange. Crossing a conditional lacZ Reporter (R26R), Cre expression from the Skt(cre) allele specifically activates β-galactosidase expression in the whole notochord from E9.

The floor plate is sufficient for development of the sclerotome and spine without the notochord.

Danforth'sshort-tail (Sd) mouse is a semi-dominant mutation affecting the development of the vertebral column. Although the notochord degenerates completely by embryonic day 9.5, the vertebral column exists up to the lumber region, suggesting that the floor plate can substitute for notochord function.

The Skt gene, required for anorectal development, is a candidate for a molecular marker of the cloacal plate.

Background And Aims: It has been reported that a dorsal cloacal plate defect is associated with anorectal malformations (ARMs); however, there has been very little information reported about the developmental mechanisms involved with cloacal plate formation. Danforth's short tail (Sd) mutant mice show ARMs. In our previous study, the co-presence of Skt ( Gt ) mutation, in which Skt gene is disrupted by the gene-trap vector (p-U8), increased the incidence of ARMs in Sd mutant to 100%.

Synoviocyte-derived angiopoietin-like protein 2 contributes to synovial chronic inflammation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarticular synovitis of the diarthrodial joints. Several proinflammatory cytokines derived from both infiltrating inflammatory cells and activated resident cells within the RA joint play a fundamental role in the processes that cause inflammation. However, anticytokine treatment is beneficial but not curative, the effects are only partial, and nonresponses are common.

Association of the tag SNPs in the human SKT gene (KIAA1217) with lumbar disc herniation.

Lumbar disc herniation (LDH) is one of the most common musculo-skeletal diseases. Recent studies have indicated that LDH has strong genetic determinants, and several susceptibility genes have been reported to associate with LDH; however, its etiology and pathogenesis still remain unclear. KIAA1217 (alias SKT, the human homolog of murine Skt [Sickle tail]) is a good candidate for an LDH susceptibility gene because SKT is specifically expressed in nucleus pulposa of intervertebral discs (IVDs) in humans and mice, and Skt(Gt) mice, which are established through a large-scale gene-trap mutagenesis, exhibit progressive, postnatal onset abnormality of the IVDs.

Early pre-implantation lethality in mice carrying truncated mutation in the RNA polymerase 1-2 gene.

Ribosomal DNA (rDNA) transcription by RNA polymerase I (Pol I) is an important initial step for the production of ribosomes. The RNA polymerase 1-2 (Rpo1-2) gene is comprised of 15 exons and encodes 1135 amino acids (aa) of the second largest subunit in Pol I. In a gene trap screen, we have identified an insertional mutation (Rpo1-2(Gt)) in the 14th exon of Rpo1-2, resulting in a truncation of 312aa from the C-terminal.

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.