Phenotypes for Nphs2 MGI:3028633 MGI Mouse

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)

decreased body size ( J:87577 )

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

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

abnormal kidney arterial blood vessel morphology ( J:87577 )

• Background Sensitivity: on a mixed genetic background, notable thickening of the arteriolar wall with several layers of alphaSMA-positive muscular cells is evident as early as day 2; in contrast, no renal arteriolar lesions are observed on a pure 129/Sv background

abnormal peritubular capillary morphology ( J:87577 )

• diffuse dilatation of peritubular capillaries as early as day 2

kidney hemorrhage ( J:87577 )

• Background Sensitivity: on a mixed genetic background, localized kidney hemorrhage (red spots) is visible at death while multiple foci of interstitial hemorrhages (primarily on the superficial cortex) are seen as early as day 2; in contrast, no hemorrhages are observed on a pure 129/Sv background

increased urine protein level ( J:87577 )

• massive proteinuria is present from birth

albuminuria ( J:87577 )

• mostly albumin

abnormal kidney cortex morphology ( J:87577 )

• multiple foci of interstitial hemorrhages primarily on the superficial cortex as early as day 2

abnormal renal glomerular capsule morphology ( J:87577 )

• failure of Bowman's capsule and glomerulus to adhere

abnormal podocyte morphology ( J:87577 )

• hypertrophied and focally vacuolized podocytes; vacuoles stain positive for albumin

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

podocyte hypertrophy ( J:87577 )

• hypertrophied podocytes

podocyte microvillus transformation ( J:87577 )

• extensive microvillus formation is apparent at E16.5 in mature glomeruli and persists after birth

abnormal renal glomerulus basement membrane morphology ( J:87577 )

• the GBM appears to be pushed outward as a result of mesangial expansion

abnormal renal glomerulus morphology ( J:87577 )

• completely sclerotic glomeruli do not adhere to the Bowman's capsule

abnormal glomerular capillary morphology ( J:87577 )

• progressively reduced patency of the capillary lumens

abnormal glomerular capillary endothelium morphology ( J:87577 )

• endothelial cell hypertrophy as early as day 2

expanded mesangial matrix ( J:87577 )

• rapid development of diffuse mesangial sclerosis first seen at day 1 and eventually involving all mature glomeruli without mesangial cell proliferation

• massive mesangial accumulation of extracellular matrix proteins including nidogen, type IV collagen, laminin, perlecan, and fibronectin, as shown by immunohistochemical analysis at day 6

• mild mesangial sclerosis in immature glomeruli of mice surviving longer than 10 days

mesangiolysis ( J:87577 )

• focal mesangiolysis progressive with age

cortical renal glomerulopathies ( J:87577 )

• Background Sensitivity: on a mixed background, rapid progression of massive diffuse mesangial sclerosis (DMS) is observed in the absence of focal segmental glomerulosclerosis (FSGS) lesions; in contrast, less rapidly progressive DMS and additional changes resembling a collapsing form of glomerulopathy are observed on a pure 129/Sv background

renal glomerulus hypertrophy ( J:87577 )

• significant enlargement of mature glomeruli due to accumulated mesangial matrix

abnormal renal tubule epithelium morphology ( J:87577 )

• vacuolization primarily of the proximal tubule epithelium

dilated proximal convoluted tubule ( J:87577 )

• proximal tubular focal dilations and vacuolized epithelium evident at day 1

renal cast ( J:87577 )

• presence of protein casts, primarily in proximal renal tubules evident at day 1

kidney failure ( J:87577 )

• death due to end-stage renal failure