Mouse Genome Informatics
hm1
    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


Mouse Genome Informatics
hm2
    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/body
• 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


Mouse Genome Informatics
cn3
    Nphs2tm1Antc/Nphs2tm3.1Antc
Tg(CAG-cre/Esr1*)86Lbgn/0

involves: 129 * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die 11 weeks after tamoxifen treatment

renal/urinary system
• after 4 weeks of tamoxifen treatment, mice develop nonselective proteinuria compared with control mice
• after 10 days of tamoxifen treatment
• after 2 weeks of nursing from mice fed tamoxifen
• after 9 weeks, tamoxifen-treated mice exhibit progressive tubular injury with basement membrane thickening and interstitial fibrosis unlike similarly treated wild-type mice
• after 9 weeks in tamoxifen-treated mice
• tamoxifen-treated mice exhibit focal effacement at 1 and 2 weeks then diffuse effacement at 4 weeks unlike similarly treated wild-type mice
• after 2 weeks of tamoxifen treatment, mice exhibit podocyte hypertrophy compared with similarly treated control mice
• after 4 weeks, tamoxifen-treated mice exhibit glomerular pseudocrescents in some glomeruli unlike in similarly treated control mice
• mice nursed by dams fed tamoxifen exhibit lesions of mesangial proliferation compared with similarly treated controls
• after 2 weeks of tamoxifen treatment, mice exhibit minimal mesangial matrix expansion compared with similarly treated control mice
• after 4 weeks of tamoxifen treatment, mice exhibit focal segmental glomerulosclerosis in many glomeruli with varying severity unlike in similarly treated control mice
• mice nursed by dams fed tamoxifen exhibit lesions of focal segmental glomerulosclerosis unlike similarly treated control mice
• glomerulosclerosis worsens by 6 weeks of tamoxifen treatment
• at or near death, tamoxifen-treated mice exhibit global scelrosis
• tamoxifen-treated mice exhibit tubulointerstitial injury with diffuse tubular dilation, tubular atrophy and necrosis, and proteinaceous casts unlike in similarly treated control mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice

homeostasis/metabolism
• after 6 weeks of tamoxifen treatment
• after 6 weeks of tamoxifen treatment
• after 4 weeks of tamoxifen treatment
• after 4 weeks of tamoxifen treatment, mice develop nonselective proteinuria compared with control mice
• after 10 days of tamoxifen treatment
• after 2 weeks of nursing from mice fed tamoxifen
• after 9 weeks in tamoxifen-treated mice

cardiovascular system
• modestly after 4 weeks of tamoxifen treatment

Mouse Models of Human Disease
OMIM IDRef(s)
Nephrotic Syndrome, Type 2; NPHS2 600995 J:166320