2001 Fiscal Year Final Research Report Summary
FUNCTIONAL ANALYSIS OF THE ANIONIC DRUG TRANSPORTERS USING KNOCKOUT MICE
| Project/Area Number |
11670100
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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 |
General pharmacology
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| Research Institution | Kyorin University |
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Principal Investigator |
INATOMI Jun KYORIN UNIVERSITY FACULTY OF MEDICINE FELLOW, 医学部, 助手 (00311960)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Michio FACULTY OF MEDICINE, KYORIN UNIVERSITY ASSOCIATE PROFESSOR, 医学部, 助教授 (40255401)
KANAI Yoshikatsu FACULTY OF MEDICINE, KYORIN UNIVERSITY PROFESSOR, 医学部, 教授 (60204533)
ENDOU Hitoshi FACULTY OF MEDICINE, KYORIN UNIVERSITY PROFESSOR, 医学部, 教授 (20101115)
KIM Do Kyung FACULTY OF MEDICINE, KYORIN UNIVERSITY FELLOW, 医学部, 助手 (40327474)
HOSOYAMADA Makoto FACULTY OF MEDICINE, KYORIN UNIVERSITY LECTURER, 医学部, 講師 (00291659)
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| Project Period (FY) |
1999 – 2001
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| Keywords | organic anion transporter1 / organic anion transporter2 / organic anion transporter3 / knockout mouse / gene targeting |
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| Research Abstract |
Living features need the mechanism to excrete their metabolites, drugs, or xenobiotics for their homeostasis. Most of these substances are included in the organic anion, and kidneys or liver have specific pathways to excrete them. Our laboratory cloned organic anion transporter 1 (OAT1), which plays the crutial role in excretion of organic anions in the kidneys. We also cloned OAT2, which is specifically expressed in the liver, or OAT3, which is expressed kidneys, liver, or brain and thoroughly investigated their transport properties. The purpose of this study is to verify the physiological roles of these transporters using the gene targeting.
We prepared cDNA libraries of mouse kidney and liver, and tried the screening of the libraries using the fragments of rat OATs as the probe and finally isolated mouse OAT1, OAT2, and OAT3. We determined their nucleotide sequence, and thoroughly investigated their transport properties using Xenopus oocyte expression system. We also analyzed their tissue distribution by Northern hybridization or immunohistochemistry.
We have prepared the targeting vectors from the genomic information, and have prepared the knock-out mice with the cooperation of the Transgenic. As the knock-out of these clones are not incompatible with life, we are now preparing the in vivo experiment or histopathological analysis of these mice. Thoroughout the in vivo experiments, the data of the in vitro experiments play the significant roles as the fundamental informations.
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