2006 Fiscal Year Final Research Report Summary
Molecular mechanisms of arhinencephaly and polydactyly manifestations in the mouse homolog of GCPS.
| Project/Area Number |
16591075
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Tottori University |
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Principal Investigator |
NARUSE Ichiro Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (20113326)
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| Co-Investigator(Kenkyū-buntansha) |
UETA Etsuko Tottori University, Faculty of Medicine, Research Associate, 医学部, 助手 (40335526)
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| Project Period (FY) |
2004 – 2006
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| Keywords | arhinencephaly / polydactyly / NTD / GCPS / Gli3 |
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| Research Abstract |
Non-treated homozygous polydactyly/arhinencephaly (Pdn/Pdn) mouse fetuses exhibited exencephaly in 16.7%. In the present study, ochratoxin A (OTA) or valproic acid (VPA) were administered to the Pdn/Pdn mouse embryos to investigate the synergistic effect between gene and environmental toxin. OTA- or VPA-treatments increased NTDs to 45.8% and 66.7% respectively in the Pdn/Pdn mouse. The responsible gene for Pdn/Pdn is Gli3. So, it was speculated that specific susceptibility for OTA and VPA in the Pdn/Pdn mouse embryos may be due to the severe depression of Gli3 gene expression. As the correlated genes of Gli3, Shh and Fgf8 gene expressions were examined by whole-mount in situ hybridization and real time PCR methods in the Pdn mouse embryos on day 9 or 10 of gestation after administration of OTA or VPA. No alteration of Shh expression was observed in the non-treated Pdn/Pdn, and OTA- or VPA-treated +/+ and Pdn/Pdn. Fgf8 signal was observed at the anterior neural ridge on day 9 and commissural plate on day 10 in the non-treated +/+. The expression patterns of Fgf8 in these area were altered in the non-treated Pdn/Pdn, and further enlarged and more intensive in the OTA- or VPA-treated Pdn/Pdn embryos. It was suggested that Fgf8 gene expression pattern was affected by the depression of Gli3, and alteration of Fgf8 gene expression was accelerated by the toxicities of OTA or VPA in the Pdn/Pdn.
From these findings, it was suggested that the synergistic effect between gene and environmental factors shown in this experiment using mouse homolog of GCPS may suggest the differences of sensitivity in the side effects of the environmental factors.
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