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Effect of genetic inactivation of Keap1 on the kidney morphogenesis in mice

Research Project

Project/Area Number 26461622
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionTokai University

Principal Investigator

NIIMURA Fumio  東海大学, 医学部, 准教授 (30282750)

Co-Investigator(Renkei-kenkyūsha) MATSUSAKA Taiji  東海大学, 医学部, 教授 (50317749)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords先天性腎尿路異常 / 水腎症 / Keap1 / Nrf2 / 抗酸化防御機構 / Cre-loxシステム / コンディショナルターゲティング / 酸化ストレス
Outline of Final Research Achievements

In our previous observation, hydronephrosis was not infrequently seen in Keap1 knockdown mice in which Keap1 expression was partially suppressed. In this study, we expected that renal morphogenesis might be severely impaired in Keap1 knockout mice in which Keap1 is completely inactivated. However, the kidneys in Keap1 knockout mice at the age of day 10 did not show any morphological abnormality except for rather reduced size, which was compatible to the reduced body weight. As previously reported, Keap1 knockout mice could not survive beyond the weaning stage. So, we generated a conditionally targeted mouse in which Keap1 is inactivated only in the renal proximal straight tubule to enable observation in much later phase of the kidney morphology. At 32 weeks of age, the conditionally knockout mice did not show any renal morphological abnormalities including hydronephrosis and cortical/medullary cysts. In conclusion, Keap1 plays only a limited role in the process of renal morphogenesis.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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