We recently identified a novel gene, termed klotho (hl) that is involved in
the development of a syndrome in mice resembling human aging. A defect of
the hi gene expression in mice leads to multiple disorders including arteri
osclerosis, osteoporosis, ectopic calcification, and skin atrophy together
with short lifespan and infertility. Patients with chronic renal failure (C
RF), develop multiple complications that are reminiscent of phenotypes obse
rved in hi mutant mice. Furthermore, the hi gene is mainly expressed in kid
ney and brain. These evidences above suggest the possible involvement of Kl
otho function in the complications arising in CRF patients. To investigate
the above possibility, we examined the kidneys of 10 clinically or histolog
ically diagnosed CRF cases. The level of kl gene expression was measured by
utilizing RNase protection assay. The expression of Klotho protein was ass
ayed by utilizing Western blot analysis and by immunohistochemistry. The le
vels of hi mRNA expression were greatly reduced in all CRF kidneys. Moreove
r, the production of Klotho protein was also severely reduced in all CRF ki
dneys. These results suggest that the decrease in hi gene expression in CRF
patients may underlie the deteriorating process of multiple complications
in the CRF patients. (C) 2001 Academic Press.