Phenotypes associated with this allele

• Allele Symbol: Nphs2^tm2.1Antc
• Allele Name: targeted mutation 2.1, Corinne Antignac
• Allele ID: MGI:4360671
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nphs2^tm2.1Antc/Nphs2^tm2.1Antc	involves: 129S2/SvPas * C57BL/6	MGI:4360672
cn2	Nphs2^tm2.1Antc/Nphs2^tm3.1Antc Tg(CAG-cre/Esr1*)86Lbgn/0	involves: 129S2/SvPas * C57BL/6 * DBA	MGI:6316681

Genotype
MGI:4360672

hm1

• Allelic Composition: Nphs2^tm2.1Antc/Nphs2^tm2.1Antc
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

mortality/aging

perinatal lethality, incomplete penetrance ( J:152878 )

• fewer than expected homozygotes are found at birth suggesting prenatal or perinatal lethality

• Background Sensitivity: following 3 backcrosses to 129S2/SvPas mice no significant perinatal or prenatal lethality is detected

postnatal lethality, complete penetrance ( J:152878 )

• median age of death is 4 days (range 1 - 40 days)

• Background Sensitivity: following 3 backcrosses to 129S2/SvPas mice the median age of death is increased to 14 days

renal/urinary system

abnormal glomerular capillary morphology ( J:152878 )

• at P12 mesangial sclerosis is present reducing the patency of capillary lumina

abnormal glomerular capillary endothelium morphology ( J:152878 )

• widening of the sub-endothelial spaces due to endothelial cell swelling is seen resulting in uneven glomerular capillary wall thickening

abnormal glomerular endothelium fenestra morphology ( J:152878 )

• endothelial fenestrae are frequently replaced by a continuous cytoplasmic layer lining the periphery of the capillary loops

dilated glomerular capillary ( J:152878 )

• at P4 focal dilations of capillary lumina are seen

kidney hemorrhage ( J:152878 )

• at P4 surface hemorrhages corresponding to focal areas of interstitial hemorrhages in the superficial cortex and juxtamedullary areas are seen in the kidneys

albuminuria ( J:152878 )

• progressive albuminuria develops quickly after birth

abnormal podocyte morphology ( J:152878 )

• villous transformation and extensive vacuolization are seen

podocyte foot process effacement ( J:152878 )

absent podocyte slit diaphragm ( J:152878 )

• in rare areas where foot processes are preserved slit diaphragms are not visible

expanded mesangial matrix ( J:152878 )

• at P4 mesangial expansion is seen

• at P12 mesangial sclerosis is present reducing the patency of capillary lumina

mesangiolysis ( J:152878 )

• at P4 focal areas of mesangiolysis are seen

• at P12 mesangiolysis is worse

• irregular edematous infiltration of the mesangial strands and focal detachment of mesangial cells are present

glomerulosclerosis ( J:152878 )

• at P12 retraction of some sclerotic glomeruli is observed without adhesions to Bowman's capsule

• diffuse and global glomerulosclerosis and severe tubulointerstitial lesions are seen at P32

abnormal renal tubule morphology ( J:152878 )

• protein droplets are seen along with focal tubular dilations

abnormal proximal convoluted tubule morphology ( J:152878 )

• tubular lesions, primarily in the proximal tubules, are associated with glomerular lesions

• tubules are dilated and contain protein casts

dilated renal tubule ( J:152878 )

• focal

dilated proximal convoluted tubule ( J:152878 )

renal cast ( J:152878 )

• dilated proximal convoluted tubules contain protein casts

homeostasis/metabolism

increased circulating creatinine level ( J:152878 )

• at P4 but not at P12

increased blood urea nitrogen level ( J:152878 )

• at P4 and P12

albuminuria ( J:152878 )

• progressive albuminuria develops quickly after birth

cardiovascular system

abnormal glomerular capillary morphology ( J:152878 )

• at P12 mesangial sclerosis is present reducing the patency of capillary lumina

abnormal glomerular capillary endothelium morphology ( J:152878 )

• widening of the sub-endothelial spaces due to endothelial cell swelling is seen resulting in uneven glomerular capillary wall thickening

abnormal glomerular endothelium fenestra morphology ( J:152878 )

• endothelial fenestrae are frequently replaced by a continuous cytoplasmic layer lining the periphery of the capillary loops

dilated glomerular capillary ( J:152878 )

• at P4 focal dilations of capillary lumina are seen

kidney hemorrhage ( J:152878 )

• at P4 surface hemorrhages corresponding to focal areas of interstitial hemorrhages in the superficial cortex and juxtamedullary areas are seen in the kidneys

Genotype
MGI:6316681

cn2

• Allelic Composition: Nphs2^tm2.1Antc/Nphs2^tm3.1Antc; Tg(CAG-cre/Esr1*)86Lbgn/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * DBA

Nphs2^tm2.1Antc/Nphs2^tm3.1Antc Tg(CAG-cre/Esr1*)86Lbgn/0 mice develop focal-segmental glomerulosclerosis

mortality/aging

premature death ( J:245693 )

• the median survival of tamoxifen-treated mice is 12 weeks

growth/size/body

decreased body weight ( J:245693 )

• mice exhibit lower body weight from week 6 onward after tamoxifen treatment

cardiovascular system

increased systemic arterial blood pressure ( J:245693 )

• blood pressure moderately increases after tamoxifen treatment

homeostasis/metabolism

increased urine creatinine level ( J:245693 )

• mice exhibit increased creatinine levels within a few days of tamoxifen treatment

increased circulating cholesterol level ( J:245693 )

• mice exhibit hypercholesterolemia 4 weeks after tamoxifen induction

decreased circulating serum albumin level ( J:245693 )

• mice exhibit hypoalbuminemia 4 weeks after tamoxifen induction

increased urine protein level ( J:245693 )

• mice develop proteinuria within a few days of tamoxifen treatment which increases to a maximum 4-5 weeks after induction and thereafter decreases gradually but remains elevated compared to controls

renal/urinary system

increased urine creatinine level ( J:245693 )

• mice exhibit increased creatinine levels within a few days of tamoxifen treatment

increased urine protein level ( J:245693 )

• mice develop proteinuria within a few days of tamoxifen treatment which increases to a maximum 4-5 weeks after induction and thereafter decreases gradually but remains elevated compared to controls

abnormal podocyte foot process morphology ( J:245693 )

• foot processes are irregularly shaped one week after tamoxifen induction, progressing to effacement

fused podocyte foot processes ( J:245693 )

• foot processes are fused one week after tamoxifen induction progressing to global fusion and effacement

podocyte foot process effacement ( J:245693 )

• in tamoxifen treated mice

decreased podocyte number ( J:245693 )

• mice show reduced podocyte number per glomerulus starting at the end of the second week after tamoxifen induction (68% of controls) to 18% of controls at 12-16 weeks

increased renal glomerulus basement membrane thickness ( J:245693 )

• glomerular basement membrane is thickened in tamoxifen-induced mice

glomerulosclerosis ( J:245693 )

• mice exhibit early glomerular sclerosis form the first week after tamoxifen induction that progresses increases until week eight when 100% of glomeruli are partially or globally sclerosed

renal interstitial fibrosis ( J:245693 )

• mice develop severe interstitial fibrosis which is visible from the first week after tamoxifen induction and increase to 12% of the total kidney area in the course of the disease

renal tubule atrophy ( J:245693 )

• mice develop tubular atrophy that is visible from the first week after tamoxifen induction

decreased creatinine clearance ( J:245693 )

• mice exhibit diminished creatinine clearance 4 weeks after tamoxifen induction

kidney failure ( J:245693 )

• mice progress to renal failure after tamoxifen-induction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nephrotic syndrome		DOID:1184		J:245693