Mouse Genome Informatics
hm
    Nphs2tm1Antc/Nphs2tm1Antc
involves: 129 * C57BL/6J
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
• although indistinguishable from wild-type at birth, homozygotes quickly became 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
• 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
• diffuse dilatation of peritubular capillaries as early as day 2
• 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
• massive proteinuria is present from birth
• mostly albumin
• multiple foci of interstitial hemorrhages primarily on the superficial cortex as early as day 2
• failure of Bowman's capsule and glomerulus to adhere
• hypertrophied and focally vacuolized podocytes; vacuoles stain positive for albumin
• 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
• hypertrophied podocytes
• extensive microvillus formation is apparent at E16.5 in mature glomeruli and persists after birth
• the GBM appears to be pushed outward as a result of mesangial expansion
• completely sclerotic glomeruli do not adhere to the Bowman's capsule
• progressively reduced patency of the capillary lumens
• endothelial cell hypertrophy as early as day 2
• 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
• focal mesangiolysis progressive with age
• 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
• significant enlargement of mature glomeruli due to accumulated mesangial matrix
• vacuolization primarily of the proximal tubule epithelium
• proximal tubular focal dilations and vacuolized epithelium evident at day 1
• presence of protein casts, primarily in proximal renal tubules evident at day 1
• death due to end-stage renal failure

cardiovascular system
• 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
• progressively reduced patency of the capillary lumens
• endothelial cell hypertrophy as early as day 2
• diffuse dilatation of peritubular capillaries as early as day 2
• 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

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