title: [Pulmonary emphysema in klotho mutant mice (deficient in klotho gene expression): klotho gene essential in postnatal pulmonary integrity].
abstract: The homozygous mutant klotho (KL-/-) mouse, which is deficient in klotho gene expression, exhibits multiple phenotypes resembling human aging that include a short life span, arteriosclerosis, osteoporosis, skin atrophy, and ectopic calcifications. Histologic examination of KL-/- mice at 4 weeks of age reveals pulmonary emphysema. The emphysematous changes are not caused by a developmental defect or hypoplasia of the lung. The lungs of heterozygous mutant klotho (KL+/-) mice show emphysematous changes and alveolar calcification which are almost identical to those in KL-/- mice. These observations indicate that the klotho gene expression is essential to maintaining normal alveolar architecture in postnatal life. Pulmonary function tests reveal prolonged expiration time in KL-/- mice. The expression of type IV collagen and surfactant protein-A mRNA is markedly upregulated in KL-/- mice, suggesting that a defect in matrix synthesis or in type II pneumocyte function, or both, may be involved in the pathogenesis of pulmonary emphysema in this mutant. Several animal strains have been reported to develop pulmonary emphysema, but the klotho mouse is unique because it simultaneously exhibits various aging phenotypes. Analysis of pulmonary emphysema in klotho mice will provide a unique insight into the relationship between pulmonary emphysema and aging.
authors.affiliation: Second Department of Internal Medicine, Gunma University School of Medicine, 3-39-22, Showa-machi, Maebashi, 371-8511, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Suga
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D005966:Glucuronidase; D000090265:Klotho Proteins; D008168:Lung / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D005966:Glucuronidase; D000090265:Klotho Proteins