Disruption of the Murine α1-Antitrypsin/Pl2 Gene
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概要
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Alpha-1-antitrypsin (α1-AT) is a member of the serine protease inhibitor family regulating numerous proteolytic processes. The genetic disorder, α1-AT deficiency, is well known as a cause of hereditary pulmonary emphysema and liver cirrhosis. To create an animal model of human α1-AT deficiency, we disrupted the major murine isoform PI2, which is similar to human α1-AT and is one of 7 α1-AT isoforms found in the mouse. The ability of the serum to inhibit the activities of human leukocyte elastase (HLE) and human chymotrypsin (CYT) was significantly lower in heterozygous mice (α1-AT/PI2 -/+) than wild-type (α1-AT/PI2 +/+) mice (73.2% vs. 100% for HLE and 67.8% vs.100% for CYT, respectively; P<0.05). The distribution of genotypes among F2 progeny was not in accordance with Mendelian distribution (P<0.01), as the percentages of wild-type, heterozygotes and homozygotes were 47.8%, 37.3% and 14.9%, respectively. Thus, it is likely that impairment of the protease inhibitor had a critical effect on fetus development. The α1-AT/PI2 deficient mouse will be a useful animal model for elucidating the function of α1-AT in fetal development, studying the mechanisms of chronic inflammatory disease and evaluating therapeutic candidates for the treatment of inflammatory disease.
- 社団法人 日本実験動物学会の論文
著者
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Noguchi Masato
Central Pharmaceutical Research Institute Pharmaceutical Frontier Research Laboratory Japan Tobacco
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KUSHI Atsuko
Central Pharmaceutical Research Institute, Pharmaceutical Frontier Research Laboratory, Japan Tobacc
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AKIYAMA Kiyotaka
Central Pharmaceutical Research Institute, Pharmaceutical Frontier Research Laboratory, Japan Tobacc
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EDAMURA Koji
Central Pharmaceutical Research Institute, Pharmaceutical Frontier Research Laboratory, Japan Tobacc
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YOSHIDA Takayuki
Central Pharmaceutical Research Institute, Pharmaceutical Frontier Research Laboratory, Japan Tobacc
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SASAI Hitoshi
Central Pharmaceutical Research Institute, Japan Tobacco Inc.
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Kushi Atsuko
Central Pharmaceutical Research Institute Pharmaceutical Frontier Research Laboratory Japan Tobacco
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Akiyama Kiyotaka
Central Pharmaceutical Research Institute Pharmaceutical Frontier Research Laboratory Japan Tobacco
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Edamura Koji
Central Pharmaceutical Research Institute Pharmaceutical Frontier Research Laboratory Japan Tobacco
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Sasai Hitoshi
Central Pharmaceutical Research Institute Japan Tobacco Inc.
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Yoshida Takayuki
Central Pharmaceutical Research Institute Pharmaceutical Frontier Research Laboratory Japan Tobacco
関連論文
- Disruption of the Murine α1-Antitrypsin/Pl2 Gene
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