Phenotypes associated with this allele

• Allele Symbol: Nphs2^tm1Antc
• Allele Name: targeted mutation 1, Corinne Antignac
• Allele ID: MGI:3028629
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nphs2^tm1Antc/Nphs2^tm1Antc	129-Nphs2^tm1Antc	MGI:3028634
hm2	Nphs2^tm1Antc/Nphs2^tm1Antc	involves: 129 * C57BL/6J	MGI:3028633
cn3	Nphs2^tm1Antc/Nphs2^tm3.1Antc Tg(CAG-cre/Esr1*)86Lbgn/0	involves: 129 * C57BL/6 * DBA	MGI:4847559

Genotype
MGI:3028634

hm1

• 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

Genotype
MGI:3028633

hm2

• Allelic Composition: Nphs2^tm1Antc/Nphs2^tm1Antc
• Genetic Background: involves: 129 * C57BL/6J

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 became 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

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

cardiovascular system

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 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

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

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

Genotype
MGI:4847559

cn3

• Allelic Composition: Nphs2^tm1Antc/Nphs2^tm3.1Antc; Tg(CAG-cre/Esr1*)86Lbgn/0
• Genetic Background: involves: 129 * C57BL/6 * DBA

mortality/aging

premature death ( J:166320 )

• mice die 11 weeks after tamoxifen treatment

renal/urinary system

increased urine protein level ( J:166320 )

• after 4 weeks of tamoxifen treatment, mice develop nonselective proteinuria compared with control mice

albuminuria ( J:166320 )

• after 10 days of tamoxifen treatment

• after 2 weeks of nursing from mice fed tamoxifen

abnormal kidney morphology ( J:166320 )

• after 9 weeks, tamoxifen-treated mice exhibit progressive tubular injury with basement membrane thickening and interstitial fibrosis unlike similarly treated wild-type mice

podocyte foot process effacement ( J:166320 )

• tamoxifen-treated mice exhibit focal effacement at 1 and 2 weeks then diffuse effacement at 4 weeks unlike similarly treated wild-type mice

podocyte hypertrophy ( J:166320 )

• after 2 weeks of tamoxifen treatment, mice exhibit podocyte hypertrophy compared with similarly treated control mice

abnormal renal glomerulus morphology ( J:166320 )

• after 4 weeks, tamoxifen-treated mice exhibit glomerular pseudocrescents in some glomeruli unlike in similarly treated control mice

increased mesangial cell number ( J:166320 )

• mice nursed by dams fed tamoxifen exhibit lesions of mesangial proliferation compared with similarly treated controls

expanded mesangial matrix ( J:166320 )

• after 2 weeks of tamoxifen treatment, mice exhibit minimal mesangial matrix expansion compared with similarly treated control mice

glomerulosclerosis ( J:166320 )

• 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

renal interstitial fibrosis ( J:166320 )

• after 9 weeks in tamoxifen-treated mice

abnormal renal tubule morphology ( J:166320 )

• tamoxifen-treated mice exhibit tubulointerstitial injury with diffuse tubular dilation, tubular atrophy and necrosis, and proteinaceous casts unlike in similarly treated control mice

renal tubular necrosis ( J:166320 )

• in tamoxifen-treated mice

renal tubule atrophy ( J:166320 )

• in tamoxifen-treated mice

dilated renal tubule ( J:166320 )

• in tamoxifen-treated mice

renal cast ( J:166320 )

• in tamoxifen-treated mice

homeostasis/metabolism

increased circulating creatinine level ( J:166320 )

• after 6 weeks of tamoxifen treatment

increased blood urea nitrogen level ( J:166320 )

• after 6 weeks of tamoxifen treatment

increased circulating cholesterol level ( J:166320 )

• after 4 weeks of tamoxifen treatment

increased urine protein level ( J:166320 )

• after 4 weeks of tamoxifen treatment, mice develop nonselective proteinuria compared with control mice

albuminuria ( J:166320 )

• after 10 days of tamoxifen treatment

• after 2 weeks of nursing from mice fed tamoxifen

cardiovascular system

increased systemic arterial systolic blood pressure ( J:166320 )

• modestly after 4 weeks of tamoxifen treatment

cellular

increased mesangial cell number ( J:166320 )

• mice nursed by dams fed tamoxifen exhibit lesions of mesangial proliferation compared with similarly treated controls

renal tubular necrosis ( J:166320 )

• in tamoxifen-treated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nephrotic syndrome		DOID:1184		J:166320