| Research Abstract |
Homozygous mutant klotho mouse (KL^<-/->), which lacks klotho gene expression, has short life span with various presenile presentations including arteriosclerosis, ectopic calcification, osteoporosis, dermal thinning, and hair loss. It also suffers from pulmonary emphysema as early as 4 weeks after birth. The gene-expression profile in KL^<-/-> lungs at 2 weeks of age were compared with that in wild-type lungs at the same age through hybridization method using Atlas Nylon Membranes in order to clarify the pathogenetic mechanism of pulmonary emphysema in this mouse strain.
The genes, which were expressed more intensively in KL^<-/-> lungs than in wild-type included : 1) caspase 3, a member of apoptosis-related genes (spot intensity ; KL^<-/-> 50 vs. wild-type : 27) , 2) radical fringe homolog precursor, which is related to a Notch signal transduction pathway and implicated in boundary determination (spot intensity ; KL^<-/-> : 83 vs. wild-type : 39), 3) activin receptor IIA (spot intensity ; KL^<-/->. 35 vs. wild-type : 16), activin receptor IIB (spot intensity ; KL^<-/-> : 34 vs. wild-type : 18), and MAD homolog 7 (spot intensity ; KL^<-/-> : 22 vs. wild-type : 9), which are related to TGF-β family protein. The genes, which were expressed less intensively in KL^<-/-> lungs than in wild-type included serine protease inhibitor 2 (spot intensity ; KL^<-/-> : 38 vs. wild-type : 66).
These findings suggest that deranged expression of the genes associated with lung development and apoptosis of pulmonary constituting cells participates in the pathogenesis of pulmonary emphysema of klotho mice. The suppression of protease inhibitor activity, which protects lungs from various injuries, is another contributing factor of it.
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