1988 Fiscal Year Final Research Report Summary
Possible involvement of antisense RNA in pathogenesis of type II citrullinemia.
| Project/Area Number |
62570120
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
SAHEKI Takeyori Department of Biochemistry, Faculty of Medicine, Kagoshima University, 医学部, 教授 (10056070)
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| Co-Investigator(Kenkyū-buntansha) |
NODA Takashi Department of Biochemistry, Faculty of Medicine, Kagoshima University, 医学部, 講師 (60136231)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Citrullinemia / Argininosuccinate synthetase / Antisense-RNA / In Situ Hybridization |
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| Research Abstract |
Deficiency of argininosuccinate synthetase (ASS), one of the urea cycle enzymes, causes citrullinemia. From the analysis of the abnormal enzymes in the liver, kidney and cultured skin fibroblasts of more than 70 cases of citrullinemia. we classified the citrullinemia into three distinct types. In type I, a low activity of the enzyme is mainly caused by abnormality in kinetic properties. In type II. the low activity is from a decrease in the enzyme protein which has normal kinetic properties. The low enzyme activity in type II citrullinemia, however, is seen only in the liver, but not in the kidney or cultured skin fibroblasts. on the other hand, no detectable enzyme activity is found in all the organ or cells tested in type III citrullinemia.
In the present study. we analyzed abnormality in mRNA in type II and III citrullinemia. In two cases of type III. low levels of ASS mRNA were found in the liver and in one case, a normal content of hepatic ASS mRNA was detected. In the latter case,
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further analysis showed that the mRNA has an about 100 base-defect in the coding region near 3' end. Together with analysis of CRM, the abnormality in the genomic DNA of the patient is probably a point mutation at the exon-intron junction which causes abnormal splicing of mRNA.
On the contrary, there were no abnormalities in hepatic ASS mRNA of type II citrullinemia concerning hepatic content, size and structure analyzed by SL nuclease. The results suggest that the pathogenesis of type II is suppressed translation or enhanced degradation of ASS. Possible involvement of antisense RNA in the mechanism of postulated suppressed translation of ASS were tested using sense Riboprobe of ASS mRNA for detection of antisense RNA in the liver of type II citrullinemia. As far as we tested. We could not find any evidence showing the presence of antisense RNA in the liver of control and type II citrullinemic patients. Further investigations will need to clarify the pathogenesis of type II citrullinemia. Less
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Research Products
(20 results)
