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Mutation of the mouse klotho gene leads to a syndrome resembling ageing


A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes. A defect in klotho gene expression in the mouse results in a syndrome that resembles human ageing, including a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema. The gene encodes a membrane protein that shares sequence similarity with the β-glucosidase enzymes. The klotho gene product may function as part of a signalling pathway that regulates ageing in vivo and morbidity in age-related diseases.

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Figure 1: Macroscopic findings of klotho mice (8 weeks old).
Figure 2: Short lifespan, growth retardation, and hypokinesis in kl/kl mice.
Figure 3: Histological analysis of kl/kl mice.
Figure 7: Rescue of the klotho mice by exogenous kl gene expression.
Figure 4: Identification of mouse klotho locus.
Figure 5: Expression of the mouse klotho gene.
Figure 6: Amino-acid sequences and primary structure of mouse KL protein and its human homologue.


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We thank E. Ozawa, T. Ishikawa, K. Hanaoka and I. Nonaka for earlier contributions to this work, T. Matsuzaki, S. Kameya and Y. Hiroi for maintaining mice, and H. Yamato and Y. Nagai for bone analyses.

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Correspondence to Makoto Kuro-o or Yo-ichi Nabeshima.

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Kuro-o, M., Matsumura, Y., Aizawa, H. et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390, 45–51 (1997).

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