Research Project
Grant-in-Aid for Young Scientists (B)
Caudal regression syndrome (CRS) is a congenital heterogeneousconstellation of caudal anomalies that includes varying degrees of agenesis of the spinalcolumn, anorectal malformations, and genitourinary anomalies(Ando T., Semba K. et al.Mech Dev. 128:129-40. 2011.). Its pathogenesis is unclear. However, it could be the resultof excessive physiologic regression of the embryonic caudal region based on analyses ofthe various mouse mutants carrying caudal agenesis. Among the mouse mutants, theDanforth’s short tail (Sd) mouse is considered a best model for human CRS. Sd is asemidominant mutation, characterized by spinal defects, urogenital defects, andanorectal malformations, thus showing phenotypic similarity to human CRS. Although Sdis known to map to mouse chromosome 2, little is known about the molecular nature of Sd.Here, we demonstrate an insertion of one type of retrotransposon near the Ptf1a gene.This resulted in ectopic expression of Ptf1a gene in the caudal region of the embryo anddownregulation of Cdx2 and its downstream targets, leading to characteristic phenotypesin Sd mouse. Thus, Sd mutant mice will provide insight into the development of the spinalcolumn, anus and kidney(Semba K. et al. PLoS Genet. 9:e1003204. 2013.).
All 2013 2012 2011 2010 Other
All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (17 results) (of which Invited: 3 results) Book (3 results) Remarks (3 results)
PLoS Genet.
Volume: Vol.9 Issue: 2 Pages: 1-17
10.1371/journal.pgen.1003204
Genesis
Volume: 50 Issue: 10 Pages: 758-765
10.1002/dvg.22035
Clinical Neuroscience.
Volume: 30 Pages: 1094-7
Mech Dev
Volume: 128 Pages: 129-40
Pediatr SurgInt.
Volume: 27 Pages: 269-73
International Journal of Experimental Pathology
Volume: 92 Issue: 4 Pages: 232-242
10.1111/j.1365-2613.2010.00758.x
Mechanisms of Development
Volume: 128 Pages: 129-140
Pediatric Surgery International
Volume: 27 Pages: 269-273
http://irda-genetics.kuma-u.jp/research/r06.html
