1997 Fiscal Year Final Research Report Summary
Genomic analysis of the causative gene for the aganglionosis rat and application of this rat to the pharmacological analysis
| Project/Area Number |
08680910
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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 |
Laboratory animal science
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| Research Institution | Nagoya City University |
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Principal Investigator |
AGUI Takashi Nagoya City University Medical School, Center for Experimental Animal Science, Associate Professor, 医学部, 助教授 (00212457)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Hirschsprung's disease / enteric ganglion / endothelin receptor / mutant rat / bone marrow-derived stromal cell / IL-6 / VIP / PACAP |
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| Research Abstract |
Expression of endothelin type B receptor (Ednrb) gene in the lung was extremely lower in aganglionosis rats compared to control rats. Further, the size of PCR products of the Ednrb cDNA were shorter in aganglionosis rats compared to that of control rats. By determining the coding sequence of the Ednrb cDNA in aganglionosis rats and comparing it with that of control rats, two kinds of deleted cDNAs were found to be present ; one is deleted between the 20th and 483rd nucleotide and another is deleted between the 213th and 483rd nucleotide. From these results, it is suggested that the cause of aganglionosis is due to a significant decrease in the Ednrb gene expression and deletion of the faintly expressed residual Ednrb mRNA.
We tried to examine a role of endothelin in the regulation of IL-6 production in the bone marrow of aganglionosis rats. However, endothelin could not augment IL-6 production by bone marrow-derived stromal cells prepared even from control normal littermates. Thus, it was impossible to examine the effect of endothelin in the bone marrow of this mutant rat. However, we could elucidate that other blood pressure-regulating hormones, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) regulate IL-6 production in the bone marrow.
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