Klotho disruption

Species: House mouse (Taxid: 10090)
Factor: Kl
Manipulation: Loss-of-Function, Knockout, Mutation
Effect:

Klotho disruption results in infertility and signs of premature ageing such as a short lifespan, arteriosclerosis, skin atrophy, osteoporosis, and emphysema. Klotho is highly expressed in brain and kidney [10631108]. The circulating form of Klotho binds to a cell-surface receptor and represses intracellular signals of insulin and IGF1. Perturbing insulin and IGF1 alleviates the aging-like phenotypes in Klotho-deficient mice [16123266]. kl/kl mice initially develop normally but exhibit growth retardation starting at 3-4 weeks of age. Their average lifespan is 61 days (none more than 100 days). These mice gradually become inactive, with reduced stride length, atrophic genital organs, thymus atrophy, arteriosclerosis (medial calcification and intimal thickening), ectopic calcification in arterial walls, osteroposis, skin atrophy, impaired maturation of gonadal cells, emphysema, reduced growth hormone-producing cells in the pituitary gland, slight hypercalcemia, and hyperphosphatemia [9363890]. kl/kl mice have decreased insulin production and increased insulin sensitivity [11016890].


References:
  • 9363890: Mutation of the mouse klotho gene leads to a syndrome resembling ageing.
  • 16123266: Suppression of aging in mice by the hormone Klotho.
  • 10631108: Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys.
  • 11016890: Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging.


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR



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