Mn-SODコンディショナルノックアウトマウスを用いた抗老化研究

• 清水 孝彦

  東京都健康長寿医療センター研究所老化機構研究チーム

• 白澤 卓二

  順天堂大学大学院医学研究科加齢制御医学講座

書誌事項

タイトル別名

• Anti-aging Research Using Mn-SOD Conditional Knockout Mice
• Mn SOD コンディショナル ノックアウト マウス オ モチイタ コウロウカ ケンキュウ

抄録

  Manganese superoxide dismutase (Mn-SOD) is a mitochondrial enzyme that converts toxic O₂^- to H₂O₂. Previous studies have reported that a systemic deficiency in Mn-SOD causes neonatal lethality in mice. Therefore, no mouse model is available for the analysis of the pathological role of O₂^- injuries in adult tissues. To explore an adult-type mouse model, we generated tissue-specific Mn-SOD conditional knockout mice using a Cre-loxp system. First, we generated liver-specific Mn-SOD-deficient mice by crossbreeding with albumin-Cre transgenic mice. Mn-SOD proteins were significantly downregulated in the liver of liver-specific Mn-SOD knockout mice. Interestingly, the mutant mice showed no obvious morphological abnormalities or biochemical alterations in the liver, suggesting a redundant or less important physiological role for Mn-SOD in the liver than previously thought. Next, we generated heart/muscle-specific Mn-SOD-deficient mice by crossbreeding with muscle creatine kinase-Cre transgenic mice. The mutant mice developed progressive dilated cardiomyopathy with specific molecular defects in mitochondrial respiration. Furthermore, skeletal muscle-specific Mn-SOD-deficient mice that had been generated by crossbreeding with human skeletal actin-Cre transgenic mice developed a severe physical disturbance associated with impaired cellular ATP metabolism. These results imply that the superoxide generated in mitochondria plays a pivotal role in the development and progression of pathologies in the heart and skeletal muscle, but not in the liver. In conclusion, we successfully generated various tissue-specific Mn-SOD conditional knockout mice that provide useful tools for the analysis of various oxidative stress-associated diseases.<br>

収録刊行物

• 薬学雑誌

  薬学雑誌 130 (1), 19-24, 2010-01-01

  公益社団法人 日本薬学会

キーワード

• manganese superoxide dismutase
• reactive oxygen species
• oxidative stress
• knockout mice

詳細情報

• CRID: 1390001206127472000
• NII論文ID: 130000152005
• NII書誌ID: AN00284903
• DOI: 10.1248/yakushi.130.19
• ISSN: 13475231
• ISSN: 00316903
• NDL書誌ID: 10527330
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10527330
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/130/1/130_1_19/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2010179999
• 本文言語コード: ja
• データソース種別:
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