We created Aldh2 inactive transgenic mouse. The mice are
backcrossed to C57BL6/J strain more than 15 generations (until 2006).
Allele Symbol:
Aldh2 tm1Kaw
Allele Name:
targeted mutation 1, Toshihiro Kawamoto
Gene Symbol: Aldh2
Gene Name: aldehyde dehydrogenase 2, mitochondrial
MGI Accession ID:
MGI:2157245
Original
Reference: J:63498
Type: Transgene induced (gene targeted)
Strain of Origin:
129P2/OlaHsd
Allele
Definition:
Mutation(s):
Disruption caused by insertion of vector
ES cell Line: E14
ES Cell Line Strain: 129P2/OlaHsd
Notes: A termination codon
and a neomycin selection cassette was inserted into exon
3. Western blot analysis on liver mitochondrial
fractions derived from homozygous mice confirmed that the protein was not
expressed at detectable levels.
Reference:
|
|
Reference |
|
Toxicology |
1, 3, 4, 6, 7, 8, 9, 11, 16 |
|
Alcoholism |
9, 12, 15 Matsumoto (coming soon) |
|
Cancer |
1, 3, 5, 12, Kunugita (coming soon) |
|
Cardiovascular |
2, 10 |
|
Basic data |
2, 6, 9, 10, 11, 12, 13, 14, 15, 16 |
1. Matsuda T, Matsumoto A, Uchida M, Kanaly R, Misaki K, Shibutani S, Kawamoto T, Kitagawa K, Nakayama KI, Tomokuni K, Ichiba M. ( in press) Increased formation of hepatic N2-ethylidene-2'-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2 knockout mice treated with ethanol. Carcinogenesis. 2007 Mar 14; [Epub ahead of print]
2. Wenzel P, Hink U, Oelze M, Seeling A, Isse T, Bruns K, Steinhoff L, Brandt M, Kleschyov AL, Schulz E, Lange K, Weiner H, Lehmann J, Lackner KJ, Kawamoto T, Munzel T, Daiber A. (2007) Number of nitrate groups determines reactivity and potency of organic nitrates: a proof of concept study in ALDH-2-/- mice. Br J Pharmacol. 150(4),526-33.
3. Ogawa M, Oyama T, Isse T, Saito K, Tomigahara Y, Endo Y, Kawamoto T. (2007) A comparison of covalent binding of ethanol metabolites to DNA according to Aldh2 genotype. Toxicol Lett. 168(2), 148-54.
4. Oyama T, Isse T, Ogawa M, Muto M, Uchiyama I, and Kawamoto T. (2007) Susceptibility to inhalation toxicity of acetaldehyde in Aldh2 knockout mice. Front Biosci. 12, 1927-1934 http://www.bioscience.org/inpress/2198.pdf.
5. Ogawa M, Isse T, Oyama T, Kunugita N, Yamaguchi T, Kinaga T, Narai R, Matsumoto A, Kim Y.D., Kim H, Uchiyama I, and Kawamoto T. (2006) Urinary 8-hydroxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) levels in Aldh2 knock-out mice under acetaldehyde exposure. Industrial Health 44, 179-183
6. Isse T, Oyama T, Matsuno K, Kitagawa K, Ogawa M, Kinaga T, Suzuki-Narai R, Yamaguchi T, Uchiyama I, and Kawamoto T. (2005) Acetaldehyde Elimination Changes in Transgenic Mice Lacking Aldehyde Dehydrogenase 2 Activity. In Enzymology and Molecular Biology of Carbonyl Metabolism 12, ISBN1-55753-384-9 Edited by Henry Weiner, Bryce Plapp, Ronald Lindahl, and Edmund Maser, Prude University Press, West Lafayette, Indiana USA
7. Isse T, Oyama T, Matsuno K, Ogawa M, Narai-Suzuki R, Yamaguchi T, Murakami T, Kinaga T, Uchiyama I, and Kawamoto T. (2005) Paired acute inhalation test revealed that acetaldehyde toxicity was higher in aldehyde dehydrogenase 2 knockout mice than in wild-type mice. J Toxicol Sci 30, 329-337
8. Isse T, Oyama T, Matsuno K, Uchiyama I, and Kawamoto T. (2005) Aldehyde dehydrogenase 2 activity affects the symptoms produced by an intraperitoneal acetaldehyde injection, but not acetaldehyde lethality. J Toxicol Sci 30, 315-328
9. Isse T, Matsuno K, Oyama T, Kitagawa K and Kawamoto T. (2005) Aldehyde dehydrogenase 2 gene targeting mouse lacking enzyme activity shows high acetaldehyde level in blood, brain and liver after ethanol gavages. Alcoholism: Clinical and Experimental Research. 29, 1959-1964
10. Chen Z, Foster MW, Zhang J, Mao L, Rockman HA, Kawamoto T, Kitagawa K, Nakayama KI, Hess DT, Stamler JS. (2005) An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation. Proc Natl Acad Sci U S A. 102(34), 12159-64.
11. Kim YD, Oyama T, Isse T, Kim H and Kawamoto T (2005) Expression levels of hepatic cytochrome p450 enzymes in Aldh2 deficient mice following ethanol exposure; a pilot study. Archives of Toxicology,79, 192-195
12. Oyama T, Isse T, Kagawa N, Kinaga T, Kim YD, Morita M, Sugio K, Weiner H, Yasumoto K, and Kawamoto T. (2005) Tissue-distribution of aldehyde dehydrogenase 2 and effects of the ALDH2 gene-disruption on the expression of enzyme involved in alcohol metabolism. Front Biosci. 10, 951-960
13. Kawamoto T, KitagawaK, Isse T, Matsumoto A, Yamaguchi T, Suzuki R, Ogawa M, Kinga T, Matsuno K, Kunugita N, Oyama T (2003) Application of aldehyde dehydrogenase 2 knockout mouse to alcohol researches. Jpn j psychiatr res alcohol 10(1), 3-10. [Japanese, review ] [川本 俊弘, 北川 恭子, 一瀬 豊日, 松本 明子, 山口 哲右, 鈴木 理恵, 小川 真規, 木長 健, 松野 康二, 欅田 尚樹, 小山 倫浩(2003) アルデヒド脱水素酵素2（Aldh2)ノックアウトマウスのアルコール医学研究への応用 日本アルコール精神医学雑誌10( 1), 3-10.]
14. Kawamoto T, Isse T, Kunugita N, Yang M, Kitagawa K, Suenaga R, Matsumoto A, Oyama T. (2003) Effects of genetic polymorphism of drug methabolizing enzymes on smoking and drinking. J UOEH. 25(supplement 1), 97-106
15. Isse T, Oyama T, Kitagawa K, Matsuno K, Matsumoto A, Yoshida A, Nakayama K, Nakayama K, Kawamoto T.(2002) Diminished alcohol preference in transgenic mice lacking aldehyde dehydrogenase activity. Pharmacogenetics. 12(8), 621-6.
16. Kitagawa K, Kawamoto T, Kunugita N, Tsukiyama T, Okamoto K, Yoshida A, Nakayama K, Nakayama K. (2000) Aldehyde dehydrogenase (ALDH) 2 associates with oxidation of methoxyacetaldehyde; in vitro analysis with liver subcellular fraction derived from human and Aldh2 gene targeting mouse. FEBS Lett. 476(3), 306-11.
Professor Toshihiro Kawamoto takes full responsibility for the wording and content of this reports.
更新日: 09/April/2007
文責：衛生学教室
連絡先：<j-eisei＠mbox.med.uoe-u.ac.jp>