Disruption of the klotho Gene Causes Pulmonary Emphysema in Mice
| Autor: | Yoshichika Sando, Yo-ichi Nabeshima, Ryozo Nagai, Tatsuo Suga, Yoshio Ohyama, Tomoyuki Kuwaki, Toshitaka Maeno, Matsumura Yutaka, Hiroki Aizawa, Yuri Maeno, Masahiko Kurabayashi, Makoto Kuro-o |
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| Rok vydání: | 2000 |
| Předmět: |
Pulmonary and Respiratory Medicine
Aging Pathology medicine.medical_specialty Clinical Biochemistry Biology Pulmonary function testing Mice Type IV collagen medicine Animals Humans Klotho Proteins Molecular Biology Klotho Glucuronidase Lung Type-II Pneumocytes Gene Expression Regulation Developmental Membrane Proteins Cell Biology Blotting Northern Mice Mutant Strains Pathophysiology Disease Models Animal medicine.anatomical_structure Animals Newborn Pulmonary Emphysema Triphosphatase Lung Volume Measurements Type I collagen |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 22:26-33 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/ajrcmb.22.1.3554 |
| Popis: | Homozygous mutant klotho (KL(-/-)) mice exhibit multiple phenotypes resembling human aging. In the present study, we focused on examining the pathology of the lungs of klotho mice and found that it closely resembled pulmonary emphysema in humans both histologically and functionally. Histology of the lung of KL(-/-) mice was indistinguishable from those of wild-type littermates up to 2 wk of age. The first histologic changes appeared at 4 wk of age, showing enlargement of the air spaces accompanied by destruction of the alveolar walls, and progressed gradually with age. In addition to these changes, we observed calcium deposits in type I collagen fibers in alveolar septa and degeneration of type II pneumocytes in 8- to 10-wk-old KL(-/-) mice. Pulmonary function tests revealed prolonged expiration time in KL(-/-) mice, which is comparable with the pathophysiology of pulmonary emphysema. The expression level of messenger RNA for type IV collagen, surfactant protein-A and mitochondrial beta-adenosine triphosphatase was significantly increased in KL(-/-) mice, which may represent a compensatory response to alveolar destruction. Additionally, the heterozygous mutant klotho mice also developed pulmonary emphysema late in life, around 120 wk of age. These findings indicate that klotho gene expression is essential to maintaining pulmonary integrity during postnatal life. The klotho mutant mouse is a useful laboratory animal model for examining the relationship between aging and pulmonary emphysema. |
| Databáze: | OpenAIRE |
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