2004 Volume 53 Issue 5 Pages 437-443
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.
Bulletin of the Experimental Animals
Proceedings of The Japanese Association of Animal Models for Human Diseases
Proceedings of The Japanese Society of Animal Models for Human Diseases
