2012 Fiscal Year Final Research Report
Elucidation for molecular etiology of Danforth's short tail (Sd)mutant, a caudal regression model mouse
| Project/Area Number |
22791388
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
SEMBA Kei 熊本大学, 生命資源研究支援センター, 特定事業研究員 (00398190)
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| Research Collaborator |
YAMAMURA Ken-ichi 熊本大学, 生命資源研究支援センター, 教授 (90115197)
ARAKI Kimi 熊本大学, 生命資源研究支援センター, 准教授 (90211705)
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| Project Period (FY) |
2010 – 2012
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| Keywords | Danforth's short tail / Sd 変異マウス / transposon / Ptf1a / 脊索 / 遺伝子破壊 / 変異 ES 細胞 / 脊椎欠損 |
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| Research Abstract |
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.).
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Research Products
(17 results)
