The wt1-heterozygous mouse; a model to study the development of glomerular sclerosis.
In the present study, it is shown that mice heterozygous for wt1 develop glomerular sclerosis and the nature and time course of events leading to the glomerular scarring are determined. Wt1-heterozygous (wt1het) mice and their wild-type littermates were closely monitored from birth and plasma levels of urea, creatinine, and albumin were compared with histological data and clinical features. One of the first indications of nephropathy in the wt1het mouse was the development of proteinuria, accompanied by progressive elevation of the plasma levels of urea and creatinine. Subsequently, the mice developed albuminuria, which correlated with thickening of the glomerular basement membrane and fusion of the podocyte foot processes. Glomerulosclerosis was a relatively late event, accompanied by severe albuminuria and loss of WT1, nephrin, CD2AP, and alpha-actinin-4.
Menke
Aswin L
AL
MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK.
IJpenberg
Annemieke
A
Fleming
Stewart
S
Ross
Allyson
A
Medine
Claire N
CN
Patek
Charles E
CE
Spraggon
Lee
L
Hughes
Jeremy
J
Clarke
Alan R
AR
Hastie
Nicholas D
ND
D000419:Albuminuria / Q000235:genetics; D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006579:Heterozygote; D007668:Kidney / Q000648:ultrastructure; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011507:Proteinuria / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014508:Urea / Q000097:blood; D025721:WT1 Proteins / Q000235:genetics*
D025721:WT1 Proteins; D014508:Urea; D003404:Creatinine