Mouse Genome Informatics
hm
    Nphs2tm1Antc/Nphs2tm1Antc
129-Nphs2tm1Antc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• Background Sensitivity: death occurs much later on a pure 129/Sv genetic background (postnatal day 23) than on a mixed genetic background involving 129/Sv and C57BL/6J (postnatal day 7.5)

growth/size/body
• although indistinguishable from wild-type at birth, homozygotes quickly become growth retarded

homeostasis/metabolism
• levels significantly elevated at death
• levels significantly elevated at death
• massive proteinuria is present from birth
• mostly albumin

renal/urinary system
N
• Background Sensitivity: absence of renal vascular lesions and interstitial hemorrhages on a pure 129/Sv genetic background; in contrast, very severe arteriolar lesions and multiple foci of interstitial hemorrhages on a mixed background involving 129/Sv and C57BL/6J (J:87577)
• massive proteinuria is present from birth
• mostly albumin
• striking podocyte vacuolization in mice exhibiting the collapsing form of glomerulopathy
• number of huge vacuolated podocytes appears increased, suggesting epithelial cell proliferation
• altered expression of several podocyte genes, inluding nephrin; nephrin labeling shifts from a linear to a granular pattern, with irregular extensions at some distance from the GBM, unlike in control mice
• foot processes are focally present but are of irregular size and shape
• extensive podocyte effacement is apparent at E16.5 in mature glomeruli and persists after birth
• focally associated with cytoplasmic vacuolization
• the remaining foot process junctions lack a visible slit diaphragm
• the slit diaphragm is replaced by irregular adhesions between adjacent cells
• glomerular lesions are most often similar to those observed on a mixed genetic background but progress less rapidly
• in addition, 2 of 14 mice exhibit retraction and collapse of the glomerular tuft lined by huge vacuolized podocytes; however, no mesangial matrix accumulation is observed in these mice
• massive mesangial sclerosis in mice with a sclerotic form of renal disease
• Background Sensitivity: less rapid progression of diffuse mesangial sclerosis (DMS) observed on a pure 129/Sv background than on a mixed genetic background involving 129/Sv and C57BL/6J
• Background Sensitivity: in addition to DMS, a collapsing form of glomerulopathy is observed in 2 of 14 mice of a pure 129/Sv background, not observed on a mixed genetic background
• Background Sensitivity: on a pure 129/Sv genetic background, superimposed crescentic lesions involving 5-40% of glomeruli are observed in a 24-day-old mouse with a collapsing form of glomerulopathy and in a 13-day-old mouse with a sclerotic form of renal disease; in contrast, no crescent formation is noted on a mixed genetic background
• proximal tubular dilations and vacuolized epithelium
• death due to end-stage renal failure

Mouse Models of Human Disease
OMIM IDRef(s)
Nephrotic Syndrome, Type 2; NPHS2 600995 J:87577