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首页> 外文期刊>Experimental Animals >Disruption of the Murine α1-Antitrypsin/PI2 Gene
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Disruption of the Murine α1-Antitrypsin/PI2 Gene

机译：小鼠α1-抗胰蛋白酶/ PI2基因的破坏。

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摘要

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 F_2 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.
机译：Alpha-1-抗胰蛋白酶（α1-AT）是丝氨酸蛋白酶抑制剂家族的成员，可调节多种蛋白水解过程。众所周知，遗传性疾病α1-AT缺乏是遗传性肺气肿和肝硬化的原因。为了创建人类α1-AT缺乏症的动物模型，我们破坏了主要的鼠类同工型PI2，其与人类α1-AT类似，并且是小鼠中发现的7种α1-AT同型之一。杂合小鼠（α1-AT/ PI2--/ +）的血清抑制人白细胞弹性蛋白酶（HLE）和胰凝乳蛋白酶（CYT）活性的能力明显低于野生型（α1-AT/ PI2 + / +）小鼠（HLE分别为73.2％与100％，CYT为67.8％与100％; P <0.05）。 F_2子代之间的基因型分布不符合孟德尔分布（P <0.01），因为野生型，杂合子和纯合子的百分比分别为47.8％，37.3％和14.9％。因此，蛋白酶抑制剂的损伤可能对胎儿发育具有关键作用。缺乏α1-AT/ PI2的小鼠将成为阐明α1-AT在胎儿发育中的功能，研究慢性炎性疾病的机制并评估治疗炎性疾病的候选药物的有用动物模型。

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