アクティブボード・２０１０年１月
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研究発表を行った学会；
・第３２回日本分子生物学会年会
　２００９年１２月９日〜１２日（横浜）

タイトル；Examination of caudal regression syndrome model mouse with disorder in spinal formation.
　
発表者；　安藤　卓　氏
　　　（熊本大学　生命資源研究・支援センター　表現型クリニック分野）

Abstract；
Caudal regression syndrome (CRS) is one of rare congenital malformation syndromes characterized by dysplasia in the lower body; deficit of lower vertebral column, kidney hypo/agenesis, anorectal malformation and so on. Details of the pathogenesis are not known though the pregnancy complicated by diabetes and the genetic factors are suggested as primary causes. We found that the phenotypes of the Danforth‘s short tail (Sd) homozygous mutant mouse, vertebral defect below the lower thoracic level, deficit of kidney, and the imperforate anus, resembled presentation of CRS. To confirm genotype of early Sd embryo, we utilized double mutant mouse; Sd and SktGt which exists near the Sd locus. In this study, we focused the process of spinal development. To investigate the process of forming vertebral bodies in the Sd SktGt mutant mice, we analyzed expression of genes associated with the spinal development (Shh, Pax1 and Uncx4.1) in E9.0-10.5 embryos. Sd SktGt double homozygous embryos show premature termination of the vertebral column in the 6th thoracic vertebral body on average. While the Uncx4.1 is expressed normally in the somites, the notochord is missing completely until E9.5.Pax1 is activated only in the regions inducing floor plate which could express Shh gene.
These results strongly suggest that the notochord degeneration preceding aberrant differentiation of somites into sclerotomes in early embryos causes developmental anomaly of the vertebrae in later embryos. It is also speculated that a dysfunction of notochord instead of abnormality in the neural tube that has been advocated may involve CRS onset.