International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Prof. Yo-ichi Nabeshima
Kyoto University Faculty of Medicine
Yoshida-Konoe-tyo Sakyo-ku

To escape from aging and aging related disorders has been one of big dreams from the beginning of the history of human being. However, our knowledge on the molecular mechanisms of aging has been limited. We recently developed a unique short life mouse strain by the insertion mutation in which a single gene mutation caused multiple aging related disorders and identified the responsible gene termed klotho after the name of one of the Fates. Klotho was a novel type 1 membrane protein of beta-glucosidase family. A processed form including almost all extra-cellular domain was secreted and found in serum. The most characteristic phenotypes of mutants seemed to be caused by the abnormality of calcium metabolism. Furthermore the klotho gene was expressed mainly in the tissues important for calcium homeostasis such as distal tubule cells of the kidney, choroid plexus in the brain, and main cells of the parathyroid grand. Indeed, serum concentrations of calcium and phosphorus in klotho mutants were significantly higher than those of wild one. As expected, the Klotho protein plays a critical role for the regulation of calcium and phosphorus homeostasis and the increased activation of vitamin D3 can be a major cause for the multiple phenotypes of klotho mutants. On going analyses of the function of Klotho will be discussed.

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