Phenotypes Associated with This Genotype

Genotype
MGI:3028634

• Allelic Composition: Nphs2^tm1Antc/Nphs2^tm1Antc
• Genetic Background: 129-Nphs2^tm1Antc

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

postnatal lethality, complete penetrance ( J:87577 )

• 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

decreased body size ( J:87577 )

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

homeostasis/metabolism

increased circulating creatinine level ( J:87577 )

• levels significantly elevated at death

increased blood urea nitrogen level ( J:87577 )

• levels significantly elevated at death

increased urine protein level ( J:87577 )

• massive proteinuria is present from birth

albuminuria ( J:87577 )

• mostly albumin

renal/urinary system

renal/urinary system phenotype ( J:87577 )

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

increased urine protein level ( J:87577 )

• massive proteinuria is present from birth

albuminuria ( J:87577 )

• mostly albumin

abnormal podocyte morphology ( J:87577 )

• 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

abnormal podocyte foot process morphology ( J:87577 )

• foot processes are focally present but are of irregular size and shape

podocyte foot process effacement ( J:87577 )

• extensive podocyte effacement is apparent at E16.5 in mature glomeruli and persists after birth

• focally associated with cytoplasmic vacuolization

absent podocyte slit diaphragm ( J:87577 )

• the remaining foot process junctions lack a visible slit diaphragm

• the slit diaphragm is replaced by irregular adhesions between adjacent cells

abnormal renal glomerulus morphology ( J:87577 )

• 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

expanded mesangial matrix ( J:87577 )

• massive mesangial sclerosis in mice with a sclerotic form of renal disease

cortical renal glomerulopathies ( J:87577 )

• 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

glomerular crescent ( J:87577 )

• 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

dilated proximal convoluted tubule ( J:87577 )

• proximal tubular dilations and vacuolized epithelium

kidney failure ( J:87577 )

• death due to end-stage renal failure

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nephrotic syndrome		DOID:1184		J:87577