| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Shosei Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (60294138)
FUJIMORI Toshihiko Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (80301274)
HOSHINO Mikio Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (70301273)
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| Research Abstract |
We recently developed a unique short life mouse strain, klotho in which a single gene mutation caused multiple aging related disorders. klotho gene encodes a novel type 1 membrane protein of β-glucosidase family and expressed mainly in kidney, brain and parathyroid grand. From the analysis of klotho mutants and the molecular function of klotho gene, the following observations have been elucidated. (1) Klotho proteins are detected in ER-Golgi apparatus, on a cell membrane and a 130 kd processed form containing almost extra-cellular domain is existed in serum. (2) Monoclonal antibodies against each of these three types of Klotho proteins were established and Klotho protein was detected by high sensitive antibodies against the 130 kd processed form. (3) β-glucosidase activity of Klotho protein has been suggested. (4) By analysing the lacZ function precisely intgrated just downstream region of translational initiation site of klotho gene, expression of klotho gene was detected at distal conboluted tubule cells in kidney, parathyroid hormon producing main cells, and choroid plexus in brain. (5) Klotho protein has been suggested to be a critical molecule for the fundamental mechanisms involved in the regulation of calcium and phosphorus homeostasis, heart rate, serum glucose concentration, sexual maturation and other maintenance system of healthy state of individuals. (6) The chromosomal localization of the human klotho was mapped to 13q12. At 13q12, where inherited premature aging syndrome and related disorders have not been assigned. 7 novel polymorphisms were howevcr identified from the klotho gene and suggested to associate with the aging related phenotypes. (7) β-klotho, a homologue of klotho was identified and β-klotho gene was predominantly expressed in liver, pancreas and white and brawn adipose tissues. The analysis of knockout mouse of β-klotho is on going.
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