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Gene Review

Kl  -  Klotho

Rattus norvegicus

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Disease relevance of Kl


High impact information on Kl


Biological context of Kl


Associations of Kl with chemical compounds

  • Administration of angiotensin II to rats decreases renal expression of klotho, an aging-related gene, and also causes abnormal iron deposition in renal cells [2].
  • Northern blot analysis showed that expression of klotho was markedly decreased by lipopolysaccharide (LPS) in vivo, suggesting that expression of klotho is affected by acute inflammatory stress [6].
  • In our previous studies, we demonstrated that the Klotho protein or its metabolites may possibly function as humoral factor(s) and protect against endothelial dysfunction because acetylcholine-mediated NO production in arteries was impaired in heterozygous klotho deficient mice (kl/+) [3].

Analytical, diagnostic and therapeutic context of Kl

  • Northern blot analysis using the rat klotho cDNA probe identified a single transcript of 5.2 kb in size expressed predominantly in the kidney, while RT-PCR detected low levels of expression also in the brain, lung, intestine, and ovaries [6].
  • Molecular cloning of rat klotho cDNA: markedly decreased expression of klotho by acute inflammatory stress [6].
  • We have previously shown that mice heterozygous for a defect in the klotho gene upon parabiosis with wild-type mice show improved endothelial function, suggesting that the klotho gene product protects against endothelial dysfunction [5].


  1. Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases. Nagai, R., Saito, Y., Ohyama, Y., Aizawa, H., Suga, T., Nakamura, T., Kurabayashi, M., Kuroo, M. Cell. Mol. Life Sci. (2000) [Pubmed]
  2. Iron chelation and a free radical scavenger suppress angiotensin II-induced downregulation of klotho, an anti-aging gene, in rat. Saito, K., Ishizaka, N., Mitani, H., Ohno, M., Nagai, R. FEBS Lett. (2003) [Pubmed]
  3. Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats. Aizawa, H., Saito, Y., Nakamura, T., Inoue, M., Imanari, T., Ohyama, Y., Matsumura, Y., Masuda, H., Oba, S., Mise, N., Kimura, K., Hasegawa, A., Kurabayashi, M., Kuro-o, M., Nabeshima, Y., Nagai, R. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  4. In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Mitani, H., Ishizaka, N., Aizawa, T., Ohno, M., Usui, S., Suzuki, T., Amaki, T., Mori, I., Nakamura, Y., Sato, M., Nangaku, M., Hirata, Y., Nagai, R. Hypertension (2002) [Pubmed]
  5. In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome. Saito, Y., Nakamura, T., Ohyama, Y., Suzuki, T., Iida, A., Shiraki-Iida, T., Kuro-o, M., Nabeshima, Y., Kurabayashi, M., Nagai, R. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  6. Molecular cloning of rat klotho cDNA: markedly decreased expression of klotho by acute inflammatory stress. Ohyama, Y., Kurabayashi, M., Masuda, H., Nakamura, T., Aihara, Y., Kaname, T., Suga, T., Arai, M., Aizawa, H., Matsumura, Y., Kuro-o, M., Nabeshima, Y., Nagail, R. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
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