Proteinuria-induced chronic kidney disease in the ICGN/Oa mice with a mutation of Tensin2 gene.
ICGN/Oa mice are used to study the pathophysiological mechanisms underlying proteinuria-induced chronic kidney disease (CKD). Recently, a mutation of tensin2 gene (Tns2) was suggested to be responsible for proteinuria in the inbred ICGN mice. We identified the wild-type (+/+), heterozygous (+/nep), and homozygous (nep/nep) ICGN/Oa mice by PCR assay. The homozygotes developed proteinuria, resulting in nephrotic syndrome (NS) as early as 5 weeks and CKD by 15 weeks. However, the heterozygotes did not show the symptoms of these renal failures. These results indicate that the homozygous tensin2 mutation is necessary for the ICGN/Oa mice to develop proteinuria-induced CKD. Furthermore, we examined the time course of tubulointerstitial fibrosis and the kinetics of tubular epithelial cells (TECs) in the ICGN/Oa mice using immunohistochemical and TUNEL assays. In the renal parenchyma of the five-week-old homozygotes, the expression of alpha-SMA and type I collagen were higher than those in the age-matched wild-type. Additionally, increased TEC proliferation was found at 5 weeks, and increased TEC apoptosis was by 15 weeks in the homozygotes. Tubulointerstitial fibrosis precedes TEC apoptosis in the proteinuria-induced CKD model mice, and that tubulointerstitial fibrosis may be the triggering event of the disease.
Kato
Takashi
T
The Institute of Experimental Animal Sciences, Osaka University Medical School, Suita, Japan.
Kurosawa
Tsutomu Miki
TM
Taketo
Makoto Mark
MM
D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology; D005355:Fibrosis / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D009154:Mutation; D009929:Organ Size; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011507:Proteinuria / Q000150:complications* / Q000473:pathology; D000070876:Tensins; D013997:Time Factors
D000070876:Tensins; D010749:Phosphoprotein Phosphatases; C511707:Tns2 protein, mouse