Phenotypes associated with this allele

• Allele Symbol: Tg(NPHS2-cre)295Lbh
• Allele Name: transgene insertion 295, Lawrence B Holzman
• Allele ID: MGI:2450359
• Summary: 34 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Jaml^tm1Fnyi/Jaml^tm1Fnyi Tg(NPHS2-cre)295Lbh/0	B6.Cg-Jaml^tm1Fnyi Tg(NPHS2-cre)295Lbh	MGI:6506861
cn2	Jaml^tm1Fnyi/Jaml^tm1Fnyi Lepr^db/Lepr^db Tg(NPHS2-cre)295Lbh/0	B6.Cg-Lepr^db Jaml^tm1Fnyi Tg(NPHS2-cre)295Lbh	MGI:6506864
cn3	Jaml^tm1Fnyi/Jaml^+ Lepr^db/Lepr^db Tg(NPHS2-cre)295Lbh/0	B6.Cg-Lepr^db Jaml^tm1Fnyi Tg(NPHS2-cre)295Lbh	MGI:6506863
cn4	Cfl1^tm1.1Wit/Cfl1^tm1.1Wit Tg(NPHS2-cre)295Lbh/0	involves: 129 * C57BL/6 * SJL	MGI:5432555
cn5	Myh9^tm1.1Gac/Myh9^tm1.1Gac Tg(NPHS2-cre)295Lbh/0	involves: 129 * C57BL/6 * SJL	MGI:5432397
cn6	Cmas^tm1.1Bwei/Cmas^tm1.1Bwei Tg(NPHS2-cre)295Lbh/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:6402523
cn7	Prkci^tm1Rfar/Prkci^tm1Rfar Tg(NPHS2-cre)295Lbh/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5446036
cn8	Agrn^tm1Rwb/Agrn^tm1Rwb Tg(NPHS2-cre)295Lbh/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3716770
cn9	Pdss2^tm1Dalg/Pdss2^tm1Dalg Tg(NPHS2-cre)295Lbh/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3805706
cn10	Lama5^tm2Jhm/Lama5^tm1Jhm Tg(NPHS2-cre)295Lbh/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL	MGI:5432560
cn11	Lama5^tm2Jhm/Lama5^tm2Jhm Tg(NPHS2-cre)295Lbh/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL	MGI:5432561
cn12	Cd2bp2^tm1.1Tbh/Cd2bp2^tm1.1Tbh Tg(NPHS2-cre)295Lbh/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6N * SJL	MGI:6392043
cn13	Ilk^tm1Star/Ilk^tm1Star Tg(NPHS2-cre)295Lbh/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5432357
cn14	Scrib^tm1.1Geno/Scrib^tm1.1Geno Tg(NPHS2-cre)295Lbh/0	involves: 129S1/SvImJ * C57BL/6 * SJL	MGI:5449169
cn15	Vhl^tm1Jae/Vhl^tm1Jae Tg(NPHS2-cre)295Lbh/?	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5432351
cn16	Tcf3^tm4Zhu/Tcf3^tm4Zhu Tg(NPHS2-cre)295Lbh/0	involves: 129S4/SvJaeSor * C57BL/6 * SJL	MGI:3715143
cn17	Myo1e^tm1Flv/Myo1e^tm1Flv Tg(NPHS2-cre)295Lbh/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:5445941
cn18	Myo1e^tm1Flv/Myo1e^tm1.1Flv Tg(NPHS2-cre)295Lbh/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:5445942
cn19	Ano1^tm2Jrr/Ano1^tm2Jrr Tg(NPHS2-cre)295Lbh/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:5569649
cn20	Lmx1b^tm4.1Rjo/Lmx1b^tm4.1Rjo Tg(NPHS2-cre)295Lbh/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3715141
cn21	Fat1^tm1.1Nsib/Fat1^+ Tg(NPHS2-cre)295Lbh/0	involves: 129/Sv * 129S4/SvJaeSor * C57BL/6 * C57BL/6J * SJL	MGI:6160428
cn22	Fat1^tm1.1Nsib/Fat1^tm1.1Nsib Tg(NPHS2-cre)295Lbh/0	involves: 129/Sv * 129S4/SvJaeSor * C57BL/6 * C57BL/6J * SJL	MGI:6160427
cn23	Rhoa^tm1Jrel/Rhoa^tm1Jrel Rhpn1^tm1Ktry/Rhpn1^tm1Ktry Tg(NPHS2-cre)295Lbh/0	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:6360618
cn24	Itgb1^tm1Efu/Itgb1^tm1Efu Tg(NPHS2-cre)295Lbh/0	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:5142307
cn25	Coq8b^tm1c(EUCOMM)Hmgu/Coq8b^tm1c(EUCOMM)Hmgu Tg(NPHS2-cre)295Lbh/0	involves: C3H * C57BL/6 * C57BL/6N * SJL	MGI:6455521
cn26	Atp6ap2^tm1.1Ics/Y Tg(NPHS2-cre)295Lbh/0	involves: C57BL/6 * C57BL/6N * SJL	MGI:5779963
cn27	Coq6^tm1c(EUCOMM)Hmgu/Coq6^tm1c(EUCOMM)Hmgu Tg(NPHS2-cre)295Lbh/0	involves: C57BL/6 * C57BL/6N * SJL	MGI:6459750
cn28	Srgap1^tm1a(KOMP)Wtsi/Srgap1^tm1a(KOMP)Wtsi Tg(NPHS2-cre)295Lbh/0	involves: C57BL/6 * C57BL/6N * SJL	MGI:7442514
cn29	Kctd1^tm1c(EUCOMM)Wtsi/Kctd1^tm1c(EUCOMM)Wtsi Tg(NPHS2-cre)295Lbh/0	involves: C57BL/6J * C57BL/6N * SJL	MGI:7657843
cn30	Kctd15^tm1c(EUCOMM)Wtsi/Kctd15^tm1c(EUCOMM)Wtsi Tg(NPHS2-cre)295Lbh/0	involves: C57BL/6J * C57BL/6N * SJL	MGI:7657844
cn31	Ldb1^tm1Witz/Ldb1^tm1Witz Tg(NPHS2-cre)295Lbh/0	involves: C57BL/6 * SJL	MGI:3715142
cn32	Itga3^tm1Son/Itga3^tm1Son Tg(NPHS2-cre)295Lbh/0	Not Specified	MGI:3691146
tg33	Tg(NPHS2-cre)295Lbh/Tg(NPHS2-cre)295Lbh	129S6.Cg-Tg(NPHS2-cre)295Lbh/BroJ	MGI:6401290
tg34	Tg(NPHS2-cre)295Lbh/0	129S6.Cg-Tg(NPHS2-cre)295Lbh/BroJ	MGI:6401289

Genotype
MGI:6506861

cn1

• Allelic Composition: Jaml^tm1Fnyi/Jaml^tm1Fnyi; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: B6.Cg-Jaml^tm1Fnyi Tg(NPHS2-cre)295Lbh

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

renal/urinary system

increased podocyte apoptosis ( J:300243 )

• in mice treated with streptozocin and fed a high-fat diet to induce diabetes to a lesser extent than in wild-type mice

abnormal urine albumin level ( J:300243 )

• mice treated with streptozocin and fed a high-fat diet to induce diabetes fail to compared with similarly treated mice

increased urine protein level ( J:300243 )

• mice treated with adriamycin to induce nephropathy exhibit lower urinary albumin excretion compared with similarly treated wild-type mice

decreased podocyte number ( J:300243 )

• in mice treated with streptozocin and fed a high-fat diet to induce diabetes to a lesser extent than in wild-type mice

glomerulosclerosis ( J:300243 )

• mice treated with adriamycin to induce nephropathy exhibit less glomerulosclerosis compared with similarly treated wild-type mice

renal glomerulus lipidosis ( J:300243 )

• in mice treated with streptozocin and fed a high-fat diet

• however, accumulation in the tubules is comparable to similarly treated wild-type mice

homeostasis/metabolism

abnormal urine albumin level ( J:300243 )

• mice treated with streptozocin and fed a high-fat diet to induce diabetes fail to compared with similarly treated mice

increased urine protein level ( J:300243 )

• mice treated with adriamycin to induce nephropathy exhibit lower urinary albumin excretion compared with similarly treated wild-type mice

decreased susceptibility to injury ( J:300243 )

• mice treated with streptozocin and fed a high-fat diet to induce diabetes exhibit decreased urine albumin level and less glomerular and podocyte injuries with reduced podocyte loss and apoptosis compared with similarly treated wild-type mice

• mice treated with adriamycin to induce nephropathy exhibit reduced injury (lower urinary albumin excretion and less glomerulosclerosis) compared with similarly treated wild-type mice

cellular

increased podocyte apoptosis ( J:300243 )

• in mice treated with streptozocin and fed a high-fat diet to induce diabetes to a lesser extent than in wild-type mice

Genotype
MGI:6506864

cn2

• Allelic Composition: Jaml^tm1Fnyi/Jaml^tm1Fnyi; Lepr^db/Lepr^db; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: B6.Cg-Lepr^db Jaml^tm1Fnyi Tg(NPHS2-cre)295Lbh

renal/urinary system

increased urine protein level ( J:300243 )

• not as severe as in mice with wild-type Jaml

abnormal podocyte morphology ( J:300243 )

• podocyte injury that is as severe as in mice with wild-type Jaml

expanded mesangial matrix ( J:300243 )

• not as severe as in mice with wild-type Jaml

renal glomerulus lipidosis ( J:300243 )

• not as severe as in mice with wild-type Jaml

homeostasis/metabolism

increased urine protein level ( J:300243 )

• not as severe as in mice with wild-type Jaml

Genotype
MGI:6506863

cn3

• Allelic Composition: Jaml^tm1Fnyi/Jaml⁺; Lepr^db/Lepr^db; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: B6.Cg-Lepr^db Jaml^tm1Fnyi Tg(NPHS2-cre)295Lbh

renal/urinary system

increased urine protein level ( J:300243 )

• intermediate but not as severe as in mice with wild-type Jaml

abnormal podocyte morphology ( J:300243 )

• podocyte injury that is as severe as in mice with wild-type Jaml

expanded mesangial matrix ( J:300243 )

• not as severe as in mice with wild-type Jaml

homeostasis/metabolism

increased urine protein level ( J:300243 )

• intermediate but not as severe as in mice with wild-type Jaml

Genotype
MGI:5432555

cn4

• Allelic Composition: Cfl1^tm1.1Wit/Cfl1^tm1.1Wit; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129 * C57BL/6 * SJL

mortality/aging

premature death ( J:165315 )

• mice exhibit a reduced life span with a median age at death of 9 months

homeostasis/metabolism

increased circulating creatinine level ( J:165315 )

• significant increase in serum creatinine levels at 6 months of age, indicating renal dysfunction

ascites ( J:165315 )

• large ascites detected at 9 months of age

increased urine protein level ( J:165315 )

• mice develop persistent proteinuria by 3 months of age

• rate of proteinuria increases modestly until 6 months and accelerates more rapidly thereafter

abnormal response to injury ( J:165315 )

• after induction of kidney podocyte injury by protamine sulfate (PS) perfusion, mutant foot processes exhibit a broadened and flattened morphology that is distinct from that in wild-type controls

• PS-treated mutant podocytes develop unusually long fine processes that project from primary, secondary, and tertiary processes, suggesting pseudovillous transformation

• PS-treated mutant podocytes fail to recover normal morphology following subsequent infusion of heparin sulfate, unlike wild-type controls

renal/urinary system

renal/urinary system phenotype ( J:165315 )

N • mice exhibit no evidence of glomerular or interstitial scarring, even at 9 months of age

increased urine protein level ( J:165315 )

• mice develop persistent proteinuria by 3 months of age

• rate of proteinuria increases modestly until 6 months and accelerates more rapidly thereafter

abnormal podocyte foot process morphology ( J:165315 )

• mice exhibit evidence of fine finger-like projections from the podocyte cell bodies and processes at 6 months of age

• foot process spreading is evident by 8 months of age

• following PS perfusion, foot processes exhibit a broadened and flattened morphology that is distinct from that in wild-type controls

podocyte microvillus transformation ( J:165315 )

• PS-treated podocytes develop unusually long fine processes that project from primary, secondary, and tertiary processes, suggesting pseudovillous transformation

• PS-treated mutant podocytes fail to recover normal morphology following subsequent infusion of heparin sulfate, unlike wild-type controls

integument

disheveled coat ( J:165315 )

• mice exhibit a scruffed appearance at 9 months of age

Genotype
MGI:5432397

cn5

• Allelic Composition: Myh9^tm1.1Gac/Myh9^tm1.1Gac; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129 * C57BL/6 * SJL

renal/urinary system

renal/urinary system phenotype ( J:173971 )

N • surprisingly, mice are viable and do not develop overt chronic kidney disease up to 9 months of age

N • no excessive proteinuria at 1-9 months of age relative to control mice

N • normal urine albumin/creatinine ratios at 3-9 months of age relative to control mice

albuminuria ( J:173971 )

• at 3, 4, and 6 weeks after adriamycin injection, mice develop significantly more albuminuria than similarly-treated control mice

fused podocyte foot processes ( J:173971 )

• after adriamycin injection, mice exhibit patches of foot process fusion, unlike similarly-treated control mice

podocyte foot process effacement ( J:173971 )

• after adriamycin injection, mice exhibit patches of severe foot process effacement, unlike similarly-treated control mice

podocyte microvillus transformation ( J:173971 )

• after adriamycin injection, mice exhibit evidence of pseudovillous transformation, unlike similarly-treated control mice

increased renal glomerulus basement membrane thickness ( J:173971 )

• after adriamycin injection, mice exhibit thickening of the basement membrane in some glomerular loops, unlike similarly-treated control mice

glomerulosclerosis ( J:173971 )

• at 6 weeks after adriamycin injection, mice develop focal and segmental glomerulosclerosis ranging from mild segmental sclerosis to severe global sclerosis, unlike similarly-treated control mice which develop foci of mild sclerosis but no globally sclerotic glomeruli

renal cast ( J:173971 )

• at 6 weeks after adriamycin injection, mice exhibit numerous proteinaceous casts, unlike similarly-treated control mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:173971 )

N • no excessive proteinuria at 1-9 months of age relative to control mice

N • normal urine albumin/creatinine ratios at 3-9 months of age relative to control mice

N • normal serum creatinine and BUN levels at 9 months of age relative to control mice

albuminuria ( J:173971 )

• at 3, 4, and 6 weeks after adriamycin injection, mice develop significantly more albuminuria than similarly-treated control mice

increased susceptibility to injury ( J:173971 )

• following injection with doxorubicin hydrochloride (adriamycin; 15 ug/g) to induce kidney podocyte injury, 9-11 month old mice develop severe proteinuria and glomerulosclerosis, unlike similarly-treated control mice

growth/size/body

growth/size/body region phenotype ( J:173971 )

N • normal body weight at 9 months of age relative to control mice

cardiovascular system

cardiovascular system phenotype ( J:173971 )

N • no significant difference in tail cuff blood pressure at 11-12 months of age relative to control mice

Genotype
MGI:6402523

cn6

• Allelic Composition: Cmas^tm1.1Bwei/Cmas^tm1.1Bwei; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

cardiovascular system

dilated glomerular capillary ( J:286022 )

• dilatation and narrowing at P42

growth/size/body

weight loss ( J:286022 )

• starting at P28

postnatal growth retardation ( J:286022 )

• starting at P28

homeostasis/metabolism

increased urine protein level ( J:286022 )

• progressive, starting around P28

immune system

tubular nephritis ( J:286022 )

• eosinophilic material in some proximal and distal tubules at P28

mortality/aging

premature death ( J:286022 )

• between postnatal weeks 6 and 8

renal/urinary system

dilated glomerular capillary ( J:286022 )

• dilatation and narrowing at P42

increased mesangial cell number ( J:286022 )

• at P42, mice exhibit mesangial cell expansion and activation in the smooth muscle cell of blood vessels, the center of the glomerular tufts (P57), and in Bowmans capsule (P42 and P57) unlike control mice

increased urine protein level ( J:286022 )

• progressive, starting around P28

tubular nephritis ( J:286022 )

• eosinophilic material in some proximal and distal tubules at P28

fused podocyte foot processes ( J:286022 )

• at P42

podocyte foot process effacement ( J:286022 )

• resulting in podocyte fusion, complete loss of slit diaphragm and microvillous transformation at P42

abnormal podocyte slit diaphragm morphology ( J:286022 )

• with reduction in mature slit diaphragm at P28

absent podocyte slit diaphragm ( J:286022 )

• at P42

podocyte microvillus transformation ( J:286022 )

• at P42

dilated renal glomerular capsule ( J:286022 )

• at P42

expanded mesangial matrix ( J:286022 )

• at P42

glomerulosclerosis ( J:286022 )

• focal segmental glomerulosclerosis (FSGS) with some glomeruli severely affected while others have no signs of pathology

• however, mice do not exhibit endothelial fenestration or altered glomeruli basement membrane morphology

renal glomerular synechia ( J:286022 )

• of glomerular tufts to Bowmans capsule with dilation of both at P42

renal fibrosis ( J:286022 )

• increased collagen deposition at P42

abnormal renal filtration rate ( J:286022 )

• reduced glomerular filtration rate at P28

cellular

increased mesangial cell number ( J:286022 )

• at P42, mice exhibit mesangial cell expansion and activation in the smooth muscle cell of blood vessels, the center of the glomerular tufts (P57), and in Bowmans capsule (P42 and P57) unlike control mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
focal segmental glomerulosclerosis		DOID:1312	OMIM:PS603278	J:286022

Genotype
MGI:5446036

cn7

• Allelic Composition: Prkci^tm1Rfar/Prkci^tm1Rfar; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

mortality/aging

premature death ( J:164628 )

• all mice are born healthy but die of renal failure within 4 to 5 weeks of birth

• however, mice appear normal up to 2 weeks after birth

growth/size/body

postnatal growth retardation ( J:164628 )

• at ~4 weeks of age, mice exhibit significant growth retardation relative to controls

renal/urinary system

increased urine protein level ( J:164628 )

• at ~4 weeks of age, mice exhibit significant proteinuria relative to controls

abnormal podocyte morphology ( J:164628 )

• at 4 weeks, nephrin expression appears reduced while the polarity protein Par3, the tight junction marker ZO-1, and the slit diaphragm molecules nephrin and podocin exhibit a significantly impaired, granular distribution along the glomerular basement membrane, unlike the linear pattern seen in wild-type controls

podocyte foot process effacement ( J:164628 )

• at ~4 weeks of age, foot processes appear globally effaced

abnormal podocyte slit junction morphology ( J:164628 )

• at ~4 weeks of age, severe junctional abnormalities are observed

abnormal podocyte slit diaphragm morphology ( J:164628 )

• at ~4 weeks of age, foot processes often display significant slit diaphragm displacement

glomerulosclerosis ( J:164628 )

• at ~4 weeks of age, mice develop segmental glomerulosclerosis

dilated renal tubule ( J:164628 )

• at ~4 weeks of age, mice exhibit renal tubule dilation

renal cast ( J:164628 )

• at ~4 weeks of age, mice exhibit proteinuric casts in the tubule system

kidney failure ( J:164628 )

• mice develop nephrotic syndrome and die of renal failure

homeostasis/metabolism

increased urine protein level ( J:164628 )

• at ~4 weeks of age, mice exhibit significant proteinuria relative to controls

Genotype
MGI:3716770

cn8

• Allelic Composition: Agrn^tm1Rwb/Agrn^tm1Rwb; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

renal/urinary system

renal/urinary system phenotype ( J:122821 )

N • when compared to normal controls, no pathological changes are detected until at least 8 months of age

N • glomerular filtration barrier is not compromised in mutants, with normal urinary protein and creatinine levels up to 10 months of age when compared to controls

abnormal renal glomerulus basement membrane morphology ( J:122821 )

• at ~4 months of age, glomerular basement membrane (GBM) abnormalities including focal thickening and epithelial protrusions of GBM material are observed in mutants

increased renal glomerulus basement membrane thickness ( J:122821 )

• focal thickening of the GBM is noted at ~4 months of age

Genotype
MGI:3805706

cn9

• Allelic Composition: Pdss2^tm1Dalg/Pdss2^tm1Dalg; Tg(NPHS2-cre)295Lbh/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

renal/urinary system

albuminuria ( J:136670 )

tubulointerstitial nephritis ( J:136670 )

• histological evidence of nephritis

abnormal renal tubule morphology ( J:136670 )

• extensive interstitial infiltration

dilated renal tubule ( J:136670 )

homeostasis/metabolism

increased circulating cholesterol level ( J:136670 )

• elevated plasma cholesterol

albuminuria ( J:136670 )

immune system

tubulointerstitial nephritis ( J:136670 )

• histological evidence of nephritis

Genotype
MGI:5432560

cn10

• Allelic Composition: Lama5^tm2Jhm/Lama5^tm1Jhm; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL

renal/urinary system

increased urine protein level ( J:185850 )

• animals show mild proteinuria early in life (3 weeks), and progress to the nephrotic range of disease

hematuria ( J:185850 )

• observed with age

tubulointerstitial nephritis ( J:185850 )

abnormal kidney morphology ( J:185850 )

• yellowing of the kidneys is observed with age

podocyte foot process effacement ( J:185850 )

abnormal renal glomerulus basement membrane morphology ( J:185850 )

• increased thickness, a moth-eated appearance and irregular contours with frequent subepithelial outpocketings are observed at late disease stages

increased renal glomerulus basement membrane thickness ( J:185850 )

expanded mesangial matrix ( J:185850 )

• observed at late stages of disease

glomerulosclerosis ( J:185850 )

• observed at late stages of disease

homeostasis/metabolism

increased circulating cholesterol level ( J:185850 )

• observed with age

decreased circulating serum albumin level ( J:185850 )

• observed with age

edema ( J:185850 )

• mice become edematous with age

increased urine protein level ( J:185850 )

• animals show mild proteinuria early in life (3 weeks), and progress to the nephrotic range of disease

hematuria ( J:185850 )

• observed with age

immune system

tubulointerstitial nephritis ( J:185850 )

Genotype
MGI:5432561

cn11

• Allelic Composition: Lama5^tm2Jhm/Lama5^tm2Jhm; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL

mortality/aging

postnatal lethality, incomplete penetrance ( J:185850 )

• some mice live only a few weeks, but others show little sign of disease (nephrotic syndrome) at 8 months

Genotype
MGI:6392043

cn12

• Allelic Composition: Cd2bp2^tm1.1Tbh/Cd2bp2^tm1.1Tbh; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6N * SJL

mortality/aging

premature death ( J:283435 )

• premature death at 15 to 30 weeks of age

renal/urinary system

increased mesangial cell number ( J:283435 )

increased urine protein level ( J:283435 )

• severe starting at 2 months of age

podocyte foot process effacement ( J:283435 )

• however, blood capillaries and fenestration of the endothelium are unchanged

glomerulosclerosis ( J:283435 )

renal cast ( J:283435 )

• in the renal tubules

growth/size/body

weight loss ( J:283435 )

• starting at 10 weeks of age

homeostasis/metabolism

increased urine protein level ( J:283435 )

• severe starting at 2 months of age

cellular

increased mesangial cell number ( J:283435 )

Genotype
MGI:5432357

cn13

• Allelic Composition: Ilk^tm1Star/Ilk^tm1Star; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

mortality/aging

decreased survivor rate ( J:129286 )

• only a few mice survive beyond 6 months of age

premature death ( J:129244 , J:129286 )

• mice exhibit a reduced life span with a median age of death at 19 weeks, and 100% mortality by 32 weeks of age (J:129244)

• mice begin to die at 10 weeks of age; most die of renal failure at ~3-4 months of age (J:129286)

growth/size/body

decreased body weight ( J:129286 )

• significantly decreased body weight first noted at 10 weeks of age

renal/urinary system

detached podocyte ( J:129244 , J:129286 )

• focal detachment from the basement membrane at 8-12 weeks of age (J:129244)

• by 10 weeks of age, podocytes are sometimes detached from the GBM and found in the lumens of dilated tubules (J:129286)

• however, no podocyte detachment is observed at 4 weeks of age (J:129286)

increased kidney apoptosis ( J:129286 )

• marked apoptosis in the tubulointerstitial area of the kidney at 10 weeks of age, unlike in control mice

increased podocyte apoptosis ( J:129286 )

• a significant number of TUNEL+ podocytes is noted in the lumens of tubules at 10 weeks of age, suggesting that detached podocytes undergo apoptotic death

• however, no podocyte detachment or apoptosis is observed at 4 weeks of age, when albuminuria is pronounced

increased urine protein level ( J:129244 , J:129286 )

• selective albuminuria first detected at 2 weeks that progresses rapidly to unselective proteinuria by 4-12 weeks of age (J:129244)

• massive proteinuria at 12 weeks of age (J:129244)

• significantly increased urine total protein at 4 and 10 weeks of age (J:129286)

albuminuria ( J:129244 , J:129286 )

• selective albuminuria first seen at 2 weeks of age (J:129244)

• albuminuria precedes the development of focal segmental glomerulosclerosis lesions (J:129244)

• dramatically increased urine albumin levels are first noted at 4 weeks of age, progressing to severe albuminuria at 10 weeks of age (J:129286)

tubulointerstitial nephritis ( J:129244 , J:129286 )

• tubulointerstitial changes with mononuclear infiltration at 12 weeks of age (J:129244)

• advanced tubulointerstitial inflammation in end-stage kidneys (J:129244)

• mild, patchy mononuclear inflammatory infiltrate in the interstitium at 10 weeks of age (J:129286)

abnormal kidney morphology ( J:129244 )

• at 16 weeks of age, nephrotic end-stage kidneys appear yellow and display a rough surface

abnormal podocyte morphology ( J:129244 , J:129286 )

• occasional prominent single podocytes, predominantly in juxtamedullary glomeruli at 2-3 weeks of age (J:129244)

• prominent podocytes in juxtamedullary glomeruli with pseudocysts and vacuolization, focal microvillous transformation, and multifocal foot process effacement at 4 weeks of age (J:129244)

• advanced vacuolization, microvillous transformation, widespread foot process effacement, and focal detachment from the basement membrane at 8-12 weeks of age (J:129244)

• at 4 weeks of age, an aberrant distribution of nephrin and alpha-actinin-4 is observed, unlike in control podocytes; however, the localization of podocin and synaptopodin remains intact (J:129286)

fused podocyte foot processes ( J:129286 )

• fused foot processes are noted at 10 weeks of age

podocyte foot process effacement ( J:129244 , J:129286 )

• multifocal foot process effacement at 4 weeks of age (J:129244)

• widespread foot process effacement at 8-12 weeks of age (J:129244)

• slight podocyte foot process effacement with a narrower slit diaphragm is occasionally seen at 2 weeks of age, prior to the onset of albuminuria (J:129286)

• marked foot process effacement is noted at 4 weeks of age, and becomes severe by 10 weeks of age (J:129286)

abnormal podocyte slit diaphragm morphology ( J:129244 , J:129286 )

• loss of slit diaphragm noted with progression to unselective proteinuria (J:129244)

• at 4 weeks of age, foot processes are adhered to GBM as continuous cytoplasmic processes, leading to the disappearance of the slit diaphragm (J:129286)

• a narrower slit diaphragm is occasionally found in some podocyte areas at 2 weeks of age (J:129286)

decreased podocyte number ( J:129286 )

• a ~70% reduction in the number of podocytes per glomerulus is first seen at 10 weeks of age

podocyte microvillus transformation ( J:129244 , J:129286 )

• focal microvillous transformation at 4 weeks of age (J:129244)

• at 4 weeks of age, massive microvilli are formed on the surface of podocytes, unlike in control podocytes (J:129286)

abnormal renal glomerulus basement membrane morphology ( J:129244 , J:129286 )

• no alterations in key GBM components (fibronectin, laminins, and collagen IV isoforms) are observed; however, alpha3-integrins are relocalized into a granular pattern along the GBM, consistent with altered integrin-mediated matrix assembly, at 3 weeks of age (J:129244)

• at 10 weeks of age, podocyte foot processes are sometimes detached from the GBM, leading to a naked GBM on the side of the Bowman space (J:129286)

• an irregular GBM shape is also observed in some areas of the glomeruli at 4 weeks of age (J:129286)

increased renal glomerulus basement membrane thickness ( J:129244 , J:129286 )

• homogeneous thickening of the GBM at 3 weeks of age (J:129244)

• true harmonic mean GBM thickness is increased by 22.6% at 3 weeks of age (J:129244)

• diffuse and irregular thickening of the GBM with electron-lucent areas at 8-12 weeks of age (J:129244)

• increased GBM thickness is observed in some areas of the glomeruli at 4 weeks of age (J:129286)

abnormal renal glomerulus morphology ( J:129286 )

• primary glomerular lesions first seen at 10 weeks of age

abnormal glomerular capillary morphology ( J:129244 )

• distorted capillaries at 4 and 12 weeks of age

expanded mesangial matrix ( J:129244 , J:129286 )

• occasional segmental mesangial expansion with increased matrix deposition at 4 weeks of age (J:129244)

• advanced mesangial expansion with increased matrix deposition at 12 weeks of age (J:129244)

• moderate to marked mesangial expansion at 10 weeks of age (J:129286)

glomerulosclerosis ( J:129244 , J:129286 )

• mice develop progressive focal segmental glomerulosclerosis (J:129244)

• advanced focal and segmental sclerotic lesions associated with tubulointerstitial changes at 8-16 weeks of age (J:129244)

• diffuse glomerulosclerosis in end-stage kidneys (J:129244)

• segmental glomerulosclerosis to global sclerosis at 10 weeks of age (J:129286)

glomerular crescent ( J:129244 )

• crescent formation at 12 weeks of age

renal glomerular synechia ( J:129244 )

• tuft adhesions to Bowman's capsule at 12 weeks of age

renal glomerulus hypertrophy ( J:129286 )

• enlarged glomerular size at 10 weeks of age

renal interstitial fibrosis ( J:129244 , J:129286 )

• at 12 and 16 weeks of age (J:129244)

• mild interstitial fibrosis at 10 weeks of age (J:129286)

renal tubule atrophy ( J:129244 )

• at 12 weeks of age

dilated renal tubule ( J:129286 )

• extensive tubular dilation distended by proteinaceous fluid and cellular debris at 10 weeks of age

abnormal glomerular filtration barrier function ( J:129244 )

• progressive filtration barrier failure

kidney failure ( J:129244 , J:129286 )

• mice die of kidney failure (J:129244)

• age-dependent deterioration of kidney function (J:129286)

homeostasis/metabolism

increased circulating creatinine level ( J:129286 )

• significantly increased serum creatinine levels at 10 but not at 4 weeks of age

increased blood urea nitrogen level ( J:129244 )

• at 12 weeks of age

increased circulating cholesterol level ( J:129244 )

• at 12 weeks of age

increased urine protein level ( J:129244 , J:129286 )

• selective albuminuria first detected at 2 weeks that progresses rapidly to unselective proteinuria by 4-12 weeks of age (J:129244)

• massive proteinuria at 12 weeks of age (J:129244)

• significantly increased urine total protein at 4 and 10 weeks of age (J:129286)

albuminuria ( J:129244 , J:129286 )

• selective albuminuria first seen at 2 weeks of age (J:129244)

• albuminuria precedes the development of focal segmental glomerulosclerosis lesions (J:129244)

• dramatically increased urine albumin levels are first noted at 4 weeks of age, progressing to severe albuminuria at 10 weeks of age (J:129286)

immune system

tubulointerstitial nephritis ( J:129244 , J:129286 )

• tubulointerstitial changes with mononuclear infiltration at 12 weeks of age (J:129244)

• advanced tubulointerstitial inflammation in end-stage kidneys (J:129244)

• mild, patchy mononuclear inflammatory infiltrate in the interstitium at 10 weeks of age (J:129286)

cardiovascular system

abnormal glomerular capillary morphology ( J:129244 )

• distorted capillaries at 4 and 12 weeks of age

cellular

detached podocyte ( J:129244 , J:129286 )

• focal detachment from the basement membrane at 8-12 weeks of age (J:129244)

• by 10 weeks of age, podocytes are sometimes detached from the GBM and found in the lumens of dilated tubules (J:129286)

• however, no podocyte detachment is observed at 4 weeks of age (J:129286)

increased kidney apoptosis ( J:129286 )

• marked apoptosis in the tubulointerstitial area of the kidney at 10 weeks of age, unlike in control mice

increased podocyte apoptosis ( J:129286 )

• a significant number of TUNEL+ podocytes is noted in the lumens of tubules at 10 weeks of age, suggesting that detached podocytes undergo apoptotic death

• however, no podocyte detachment or apoptosis is observed at 4 weeks of age, when albuminuria is pronounced

Genotype
MGI:5449169

cn14

• Allelic Composition: Scrib^tm1.1Geno/Scrib^tm1.1Geno; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S1/SvImJ * C57BL/6 * SJL

renal/urinary system

renal/urinary system phenotype ( J:190169 )

N • no abnormalities in renal glomerular structure or function

Genotype
MGI:5432351

cn15

• Allelic Composition: Vhl^tm1Jae/Vhl^tm1Jae; Tg(NPHS2-cre)295Lbh/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

mortality/aging

premature death ( J:162099 )

• premature death beginning at ~6 months of age in mice with the highest levels of albuminuria (>1000 ug/ml)

• however, nonproteinuric mice survive to >1 year of age without overt health problems

renal/urinary system

renal/urinary system phenotype ( J:162099 )

N • at P5, all mice exhibit normal comma and S-shaped nephric figures as well as normal capillary loop stage and maturing stage glomeruli relative to wild-type controls

N • no changes in peritubular microvessels or larger arterioles and veins are observed

dilated glomerular capillary ( J:162099 )

• dilated glomerular capillary lumen noted in mice with severe albuminuria as early as 4 weeks of age

increased mesangial cell number ( J:162099 )

• mesangial hypercellularity noted in mice with severe albuminuria at 4 weeks of age

albuminuria ( J:162099 )

• at 4 weeks of age, mice exhibit varying levels of albuminuria ranging from no detectable albumin to >1000 ug/ml in severe cases

• 54% of mice (males and females) are nonproteinuric with albumin levels ranging from 2.9 to 29.7 ug/ml, similar to those in wild-type controls

dilated kidney collecting duct ( J:162099 )

• dilated medullary collecting ducts noted in nonproteinuric mice at 4 weeks of age

podocyte foot process effacement ( J:162099 )

• podocyte foot process broadening noted in all nonproteinuric mice at 4 weeks of age

decreased podocyte number ( J:162099 )

• significant decrease in podocyte number noted in both proteinuric and nonproteinuric mice at 4 weeks of age, as shown WT1 staining

abnormal renal glomerulus basement membrane morphology ( J:162099 )

• incompletely fused or fragmented GBM noted on the subendothelial side of the capillary loop in nonproteinuric mice at 4 weeks of age

increased renal glomerulus basement membrane thickness ( J:162099 )

• abnormal GBM thickenings with numerous subepithelial "humps" and subendothelial matrix projections noted in nonproteinuric mice at 4 weeks of age

• at 16 weeks of age, overall GBM thickness in nonproteinuric mice increases to ~100 nm more than in wild-type controls

• ectopic deposition of collagen alpha1alpha2alpha1(IV) noted in GBM humps beneath podocytes

expanded mesangial matrix ( J:162099 )

• mesangial matrix expansion noted in mice with severe albuminuria at 4 weeks of age

• slightly increased mesangial matrix noted in nonproteinuric mice at 4 weeks of age

glomerular crescent ( J:162099 )

• glomerular crescents noted in mice with severe albuminuria at 4 weeks of age

renal glomerulus fibrosis ( J:162099 )

• severely fibrotic glomeruli noted in mice with massive albuminuria at 25 weeks of age

renal interstitial fibrosis ( J:162099 )

• noted in mice with severe albuminuria at 25 weeks of age

dilated renal tubule ( J:162099 )

• dilated tubules containing proteinaceous casts and cellular debris noted in mice with severe albuminuria at 25 weeks of age

• occasional dilated tubules in nonproteinuric mice at 4 weeks of age

renal cast ( J:162099 )

• proteinaceous casts detected in dilated tubules of mice with severe albuminuria at 25 weeks of age

• proteinaceous casts also noted in dilated medullary collecting ducts of nonproteinuric mice at 4 weeks of age

kidney failure ( J:162099 )

• end-stage renal failure observed in mice with the highest levels of albuminuria

homeostasis/metabolism

increased blood urea nitrogen level ( J:162099 )

• at 33-41-weeks of age, increased BUN levels are noted in association with only the highest levels of albuminuria (>1000 ug/ml)

• severely nephrotic mice show a 6-fold increase in BUN levels relative to mice with lower levels of albuminuria

edema ( J:162099 )

• edema noted in mice with the highest levels of albuminuria

albuminuria ( J:162099 )

• at 4 weeks of age, mice exhibit varying levels of albuminuria ranging from no detectable albumin to >1000 ug/ml in severe cases

• 54% of mice (males and females) are nonproteinuric with albumin levels ranging from 2.9 to 29.7 ug/ml, similar to those in wild-type controls

growth/size/body

cachexia ( J:162099 )

• wasting noted in mice with the highest levels of albuminuria

cardiovascular system

dilated glomerular capillary ( J:162099 )

• dilated glomerular capillary lumen noted in mice with severe albuminuria as early as 4 weeks of age

cellular

increased mesangial cell number ( J:162099 )

• mesangial hypercellularity noted in mice with severe albuminuria at 4 weeks of age

Genotype
MGI:3715143

cn16

• Allelic Composition: Tcf3^tm4Zhu/Tcf3^tm4Zhu; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * SJL

normal phenotype

no abnormal phenotype detected ( J:122505 )

• mice survive for at least 6 months without displaying any signs of renal failure, albuminuria, or structural alterations in podocytes or glomerular basement membrane

Genotype
MGI:5445941

cn17

• Allelic Composition: Myo1e^tm1Flv/Myo1e^tm1Flv; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

renal/urinary system

albuminuria ( J:188500 )

• on a predominantly C57BL/6 background, many mice develop albuminuria by 8 weeks of age

• however, some mice that retain Myo1e expression in podocytes, as confirmed by immunostaining, do not exhibit albuminuria; a number of these maintain normal urinary protein excretion up to 6-8 months of age

abnormal podocyte foot process morphology ( J:188500 )

• by 4 months of age, the average number of foot processes per unit length of the basement membrane is lower than that in controls

podocyte foot process effacement ( J:188500 )

• at 2 months of age, proteinuric mice exhibit only a few areas of foot process effacement

• by 4 months of age, pronounced foot process effacement is observed, unlike in control mice

abnormal renal glomerulus basement membrane morphology ( J:188500 )

• by 4 months of age, the overall outline of the GBM appears jagged and uneven, unlike in control mice

increased renal glomerulus basement membrane thickness ( J:188500 )

• at 2 months of age, proteinuric mice exhibit only a few areas of GBM thickening

• by 4 months of age, average GBM thickness is increased relative to that in controls

glomerulosclerosis ( J:188500 )

• at 8 months of age, mice exhibit some sclerotic glomeruli, unlike control mice

• however, no glomerulosclerosis is seen at 4 months

renal cast ( J:188500 )

• at 8 months of age, mice exhibit a few proteinaceous casts, unlike control mice

• however, no renal casts are seen at 4 months

homeostasis/metabolism

albuminuria ( J:188500 )

• on a predominantly C57BL/6 background, many mice develop albuminuria by 8 weeks of age

• however, some mice that retain Myo1e expression in podocytes, as confirmed by immunostaining, do not exhibit albuminuria; a number of these maintain normal urinary protein excretion up to 6-8 months of age

Genotype
MGI:5445942

cn18

• Allelic Composition: Myo1e^tm1Flv/Myo1e^tm1.1Flv; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

renal/urinary system

albuminuria ( J:188500 )

• on a predominantly C57BL/6 background, mice develop moderate albuminuria by 8 weeks of age, while control mice show no evidence of albuminuria up to 6 months of age

• however, at 2-6 months of age, mice exhibit significantly lower albumin:creatinine ratios than those observed in Myo1e^tm1.1Flv homozygotes

glomerulosclerosis ( J:188500 )

• at 7 months of age, mice exhibit some sclerotic glomeruli, unlike control mice

renal cast ( J:188500 )

• at 7 months of age, mice exhibit a few proteinaceous casts, unlike control mice

homeostasis/metabolism

albuminuria ( J:188500 )

• on a predominantly C57BL/6 background, mice develop moderate albuminuria by 8 weeks of age, while control mice show no evidence of albuminuria up to 6 months of age

• however, at 2-6 months of age, mice exhibit significantly lower albumin:creatinine ratios than those observed in Myo1e^tm1.1Flv homozygotes

Genotype
MGI:5569649

cn19

• Allelic Composition: Ano1^tm2Jrr/Ano1^tm2Jrr; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

renal/urinary system

renal/urinary system phenotype ( J:210158 )

N • mice exhibit normal glomerular filters, podocytes, numbers of reabsorption vesicles in proximal tubular epithelial cells, glomerular filtration rate and urine electrolyte excretion

Genotype
MGI:3715141

cn20

• Allelic Composition: Lmx1b^tm4.1Rjo/Lmx1b^tm4.1Rjo; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:122505 )

• most mice do not live past 14 days after birth

renal/urinary system

albuminuria ( J:122505 )

• severe within 5 days postnatal

abnormal podocyte foot process morphology ( J:122505 )

• loss of podocyte foot processes is observed at 5 days, becoming more prominent by 11 days after birth

podocyte foot process effacement ( J:122505 )

• foot process effacement is apparent by 11 days after birth

absent podocyte slit diaphragm ( J:122505 )

• loss of slit diaphragms between podocytes is observed by 11 days after birth

increased renal glomerulus basement membrane thickness ( J:122505 )

• thickening of the glomerular basement membrane is observed by 11 days after birth

abnormal renal glomerulus morphology ( J:122505 )

glomerulosclerosis ( J:122505 )

• by 11 days after birth, kidneys develop a focal-segmental glomerulosclerosis

renal glomerular synechia ( J:122505 )

• adhesions between the glomerular tuft and Bowman's capsule are seen in kidneys at 11 days

dilated renal tubule ( J:122505 )

• occasional dilated tubular profiles at 5 days of age

renal cast ( J:122505 )

• occasional dilated tubules filled with an eosinophilic, probably proteinaceous material at 5 days of age

kidney failure ( J:122505 )

• mice die from renal failure

homeostasis/metabolism

albuminuria ( J:122505 )

• severe within 5 days postnatal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nail-patella syndrome		DOID:9467	OMIM:161200	J:122505

Genotype
MGI:6160428

cn21

• Allelic Composition: Fat1^tm1.1Nsib/Fat1⁺; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129/Sv * 129S4/SvJaeSor * C57BL/6 * C57BL/6J * SJL

homeostasis/metabolism

albuminuria ( J:234732 )

• mice develop a very mild albuminuria

renal/urinary system

albuminuria ( J:234732 )

• mice develop a very mild albuminuria

abnormal glomerular mesangium morphology ( J:234732 )

• mice show only mild mesangial expansion

Genotype
MGI:6160427

cn22

• Allelic Composition: Fat1^tm1.1Nsib/Fat1^tm1.1Nsib; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129/Sv * 129S4/SvJaeSor * C57BL/6 * C57BL/6J * SJL

homeostasis/metabolism

increased urine protein level ( J:234732 )

• adults develop progressive proteinuria with massive albuminuria at 40 months of age

albuminuria ( J:234732 )

• massive albuminuria is seen at 40 months of age, about 60-fold higher than in controls

• however, serum albumin is not different

renal/urinary system

increased urine protein level ( J:234732 )

• adults develop progressive proteinuria with massive albuminuria at 40 months of age

albuminuria ( J:234732 )

• massive albuminuria is seen at 40 months of age, about 60-fold higher than in controls

• however, serum albumin is not different

abnormal podocyte morphology ( J:234732 )

• adults show collapsed F-actin in podocytes

• cell junctions of effaced foot processes resemble tight junctions

podocyte foot process effacement ( J:234732 )

• adults show widespread foot process effacement

abnormal podocyte slit diaphragm morphology ( J:234732 )

• newborns exhibit persistence of cuboidal podocytes, wide foot processes and tight-junction-like cell junctions in lieu of slit-diaphragms

• slit-diaphragms are decreased in adults

podocyte microvillus transformation ( J:234732 )

• adults show microvillar transformation

glomerulosclerosis ( J:234732 )

• adults exhibit focal segmental glomerulosclerosis, with the presence of protein casts and tubulointerstitial nephropathy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nephrotic syndrome		DOID:1184		J:234732

Genotype
MGI:6360618

cn23

• Allelic Composition: Rhoa^tm1Jrel/Rhoa^tm1Jrel; Rhpn1^tm1Ktry/Rhpn1^tm1Ktry; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * SJL

growth/size/body

decreased body weight ( J:276466 )

• reduced body weight by 3 months of age

homeostasis/metabolism

increased circulating creatinine level ( J:276466 )

renal/urinary system

abnormal kidney morphology ( J:276466 )

• mice exhibit a more severe kidney injury than single Rhpn1 homozygotes

podocyte foot process effacement ( J:276466 )

• complete podocyte effacement

glomerulosclerosis ( J:276466 )

• segmental and global focal segmental glomerulosclerosis

renal interstitial fibrosis ( J:276466 )

dilated renal tubule ( J:276466 )

renal cast ( J:276466 )

• protein casts

Genotype
MGI:5142307

cn24

• Allelic Composition: Itgb1^tm1Efu/Itgb1^tm1Efu; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * SJL

mortality/aging

premature death ( J:135414 )

• only 10% of mice survived to 6 weeks of age

• 90% of mice were euthanized at 4-5 weeks of age due to end stage renal failure and nephrotic syndrome

behavior/neurological

decreased locomotor activity ( J:135414 )

• mice become less physically active at 3 weeks of age

growth/size/body

decreased body size ( J:135414 )

• at 6 weeks of age, mice are smaller than control littermates

homeostasis/metabolism

edema ( J:135414 )

• mice develop severe edema at 3 weeks of age

increased urine protein level ( J:135414 )

• mice develop severe proteinuria by 6 weeks of age

albuminuria ( J:135414 )

• albuminuria is already evident at P1

• marked albuminuria is noted at 6 weeks of age

renal/urinary system

increased podocyte apoptosis ( J:135414 )

• a significant increase in podocyte apoptosis is detected at P10 and P21 by TUNEL analysis

• at P21, mice exhibit about one-third of the podocyte number found in control littermates, as quantified in EM sections

increased urine protein level ( J:135414 )

• mice develop severe proteinuria by 6 weeks of age

albuminuria ( J:135414 )

• albuminuria is already evident at P1

• marked albuminuria is noted at 6 weeks of age

abnormal kidney morphology ( J:135414 )

• mice develop end stage kidney disease with pathological changes in the glomeruli and tubulo-interstitium

abnormal renal glomerular capsule morphology ( J:135414 )

• at 6 weeks of age, many Bowmans capsules are either empty or contain partially degenerated glomeruli

podocyte foot process effacement ( J:135414 )

• foot process effacement is first noted at E15.5

• extensive foot process effacement is noted at P10 and progresses by P21

abnormal renal glomerulus basement membrane morphology ( J:135414 )

• early segmental splitting of the glomerular basement membrane (GBM) is first noted at P10 and progresses by P21

• however, normal GBM morphogenesis is noted at E15.5 and at P1

abnormal renal glomerulus morphology ( J:135414 )

• at P21, mice exhibit degeneration of the capillary loops and mesangium with little glomerulosclerosis

• at 6 weeks of age, mice exhibit dilated glomerular capillaries and glomerular disintegration

abnormal glomerular capillary morphology ( J:135414 )

• by P21, mice exhibit degeneration of the capillary loops

• however, normal glomerular capillary morphogenesis is noted at E15.5 and at P1

dilated glomerular capillary ( J:135414 )

• at P10, some glomeruli display segmentally "ballooned" capillary lumens; more "ballooned" capillary loops are noted at 3 weeks of age

• at 6 weeks of age, mice exhibit dilated glomerular capillaries

increased mesangial cell number ( J:135414 )

• mesangium hypercellularity is observed by 3 weeks of age

expanded mesangial matrix ( J:135414 )

• increased mesangial matrix with focal defects is noted at 3 weeks, indicating mesangial injury

mesangiolysis ( J:135414 )

• multiple cytoplasmic vacuoles are first noted in mesangial cells at P10

• by P21, mice exhibit degeneration of the mesangium with little glomerulosclerosis

abnormal renal tubule epithelium morphology ( J:135414 )

• at P10, mice exhibit multiple cytoplasmic vacuoles within the tubular epithelial cells

• flattened epithelial cells with extensive proteinaceous tubular casts are noted at 6 weeks of age

small kidney ( J:135414 )

• at 6 weeks of age, end stage kidneys are smaller than those of age-matched control mice

dilated renal tubule ( J:135414 )

• dilated renal tubules containing hyaline material are observed at 6 weeks of age

• tubular dilatation is first evident at P10 and increased by 3 weeks of age

renal cast ( J:135414 )

• extensive proteinaceous tubular casts are noted at 6 weeks of age

pale kidney ( J:135414 )

• at 6 weeks of age, end stage kidneys are paler than those of age-matched control mice

cardiovascular system

abnormal glomerular capillary morphology ( J:135414 )

• by P21, mice exhibit degeneration of the capillary loops

• however, normal glomerular capillary morphogenesis is noted at E15.5 and at P1

dilated glomerular capillary ( J:135414 )

• at P10, some glomeruli display segmentally "ballooned" capillary lumens; more "ballooned" capillary loops are noted at 3 weeks of age

• at 6 weeks of age, mice exhibit dilated glomerular capillaries

cellular

increased mesangial cell number ( J:135414 )

• mesangium hypercellularity is observed by 3 weeks of age

increased podocyte apoptosis ( J:135414 )

• a significant increase in podocyte apoptosis is detected at P10 and P21 by TUNEL analysis

• at P21, mice exhibit about one-third of the podocyte number found in control littermates, as quantified in EM sections

Genotype
MGI:6455521

cn25

• Allelic Composition: Coq8b^{tm1c(EUCOMM)Hmgu}/Coq8b^{tm1c(EUCOMM)Hmgu}; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6N * SJL

behavior/neurological

hunched posture ( J:294296 )

• from age 9 months

cellular

increased mitochondrial number ( J:294296 )

• in glomerular podocytes as mice age 10 months

increased mitochondrial size ( J:294296 )

• in glomerular podocytes as mice age 10 months

homeostasis/metabolism

increased blood urea nitrogen level ( J:294296 )

• from age 7 months

• increase in creatinine-albumin ratio from age 5 months

decreased circulating serum albumin level ( J:294296 )

• from age 5 months

• increase in creatinine-albumin ratio from age 5 months

increased circulating serum albumin level ( J:294296 )

• increase in creatinine-albumin ratio from age 5 months

integument

abnormal coat appearance ( J:294296 )

• seedy fur from age 9 months

mortality/aging

premature death ( J:294296 )

• from age 9 months

renal/urinary system

abnormal podocyte morphology ( J:294296 )

• at age 10 months

podocyte foot process effacement ( J:294296 )

• at age 10 months

abnormal podocyte slit junction morphology ( J:294296 )

• significantly reduced number of filtration-slit units per micrometer of basement membrane at age 10 months

glomerulosclerosis ( J:294296 )

• global and focal segmental glomerulosclerosis at age 10 months

renal interstitial fibrosis ( J:294296 )

• at age 10 months

small kidney ( J:294296 )

• at age 10 months

renal tubule atrophy ( J:294296 )

• at age 10 months

pale kidney ( J:294296 )

• at age 10 months

kidney failure ( J:294296 )

Genotype
MGI:5779963

cn26

• Allelic Composition: Atp6ap2^tm1.1Ics/Y; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:232697 )

♂ • between 2 and 3 weeks after birth

renal/urinary system

increased podocyte apoptosis ( J:232697 )

♂

increased urine protein level ( J:232697 )

♂ • by 14 days

albuminuria ( J:232697 )

♂ • at P2

abnormal podocyte morphology ( J:232697 )

♂ • impaired vacuolar acidification with abnormal cytoskeleton organization and cell death

podocyte foot process effacement ( J:232697 )

♂

abnormal renal tubule epithelium morphology ( J:232697 )

♂ • massive protein enrichment

absent proximal convoluted tubule brush border ( J:232697 )

♂

dilated renal tubule ( J:232697 )

♂

renal cast ( J:232697 )

♂ • protein casts in renal tubules

homeostasis/metabolism

impaired autophagy ( J:232697 )

♂ • impaired in podocytes

increased circulating creatinine level ( J:232697 )

♂ • by 14 days

increased blood urea nitrogen level ( J:232697 )

♂ • by 14 days

increased circulating cholesterol level ( J:232697 )

♂ • by 14 days

decreased circulating serum albumin level ( J:232697 )

♂ • by 14 days

increased urine protein level ( J:232697 )

♂ • by 14 days

albuminuria ( J:232697 )

♂ • at P2

cellular

abnormal cell cytoskeleton morphology ( J:232697 )

♂ • impaired vacuolar acidification with abnormal cytoskeleton organization and cell death

impaired autophagy ( J:232697 )

♂ • impaired in podocytes

increased podocyte apoptosis ( J:232697 )

♂

Genotype
MGI:6459750

cn27

• Allelic Composition: Coq6^{tm1c(EUCOMM)Hmgu}/Coq6^{tm1c(EUCOMM)Hmgu}; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * SJL

mortality/aging

moribund ( J:278754 )

• mice become moribund at 10 months of age with advanced decline of kidney function

premature death ( J:278754 )

• untreated mice exhibit 50% mortality by 10 months of age; median survival is 306 days

• treatment with 2,4-Dihydroxybenzoic acid (2,4-diHB, an analog of a CoQ precursor molecule) prevents disease progression, resulting in normal survival range

behavior/neurological

hunched posture ( J:278754 )

• hunched posture at >10 months of age

• treatment with 2,4-diHB ameliorates physical condition

integument

disheveled coat ( J:278754 )

• scruffy fur at >10 months of age

• treatment with 2,4-diHB ameliorates physical condition

renal/urinary system

abnormal glomerular capillary morphology ( J:278754 )

• obliteration of glomerular capillary lumens at 10 months of age

increased urine protein level ( J:278754 )

• males are more susceptible to proteinuria than females

albuminuria ( J:278754 )

• 7.4-fold increase in the albumin-to-creatinine ratio at 5 months of age

• up to 46.9-fold increase in albuminuria at 10 months of age

• treatment with 2,4-diHB protects mice from developing proteinuria

abnormal podocyte morphology ( J:278754 )

• podocytes appear to contain abnormal mitochondria characterized by hyperproliferation and increased size at >10 months of age

podocyte foot process effacement ( J:278754 )

• podocyte foot process effacement first observed at 5 months of age, becoming more severe by 10 months of age

• treatment with 2,4-diHB results in normal foot process morphology

abnormal podocyte slit junction morphology ( J:278754 )

• significantly reduced number of filtration slit units per micrometer of basement membrane at >10 months of age

• treatment with 2,4-diHB results in normal filtration slit morphology

decreased podocyte number ( J:278754 )

• significant reduction in expression of podocyte-specific proteins and number of WT1+ podocytes at >10 months of age, suggesting depletion of podocytes

increased renal glomerulus basement membrane thickness ( J:278754 )

• significant thickening of the glomerulus basement membrane at 10, but not at 5, months of age

glomerulosclerosis ( J:278754 )

• mild focal glomerular sclerosis at 5 months of age, becoming more severe with an increased number of sclerotic glomeruli (93.87%) by 10 months of age

• treatment with 2,4-diHB mitigates the sclerotic phenotype (4.95%) and results in normal histologic kidney morphology

renal glomerulus fibrosis ( J:278754 )

• significantly increased expression of fibrotic markers (alphaSMA, desmin, and collagen IV) in the glomeruli, typical of mesangial fibrosis, at >10 months of age

renal interstitial fibrosis ( J:278754 )

• extensive tubulointerstitial fibrosis at 10 months of age

small kidney ( J:278754 )

• kidneys appear smaller than normal upon necropsy at 10 months of age

• treatment with 2,4-diHB rescues macroscopic appearance of kidneys

renal tubule atrophy ( J:278754 )

• renal tubule atrophy at >10 months of age

dilated renal tubule ( J:278754 )

• proteinaceous casts in dilated tubules at >10 months of age

renal cast ( J:278754 )

• occasional protein casts in proximal tubules at 5 months of age

pale kidney ( J:278754 )

• kidneys appear pale upon necropsy at 10 months of age

• treatment with 2,4-diHB rescues macroscopic appearance of kidneys

homeostasis/metabolism

increased urine protein level ( J:278754 )

• males are more susceptible to proteinuria than females

albuminuria ( J:278754 )

• 7.4-fold increase in the albumin-to-creatinine ratio at 5 months of age

• up to 46.9-fold increase in albuminuria at 10 months of age

• treatment with 2,4-diHB protects mice from developing proteinuria

cellular

increased mitochondrial number ( J:278754 )

• increased number of mitochondria in podocytes at >10 months of age

increased mitochondrial size ( J:278754 )

• enlarged mitochondria in podocytes at >10 months of age

abnormal mitochondrial physiology ( J:278754 )

• increased size and number of mitochondria in podocytes at >10 months of age, indicating impaired mitochondrial function

cardiovascular system

abnormal glomerular capillary morphology ( J:278754 )

• obliteration of glomerular capillary lumens at 10 months of age

Genotype
MGI:7442514

cn28

• Allelic Composition: Srgap1^{tm1a(KOMP)Wtsi}/Srgap1^{tm1a(KOMP)Wtsi}; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * SJL
• Cell Lines: EPD0153_3_C10

renal/urinary system

renal/urinary system phenotype ( J:333727 )

N • unchallenged mice exhibit no overt renal phenotype up to 24 weeks of age, as assessed by measurement of albuminuria and histology

increased mesangial cell number ( J:333727 )

• increased mesangial cell proliferation in response to doxorubicin-induced podocyte injury

albuminuria ( J:333727 )

• increased urinary albumin-creatinine ratio in response to doxorubicin-induced podocyte injury

glomerulosclerosis ( J:333727 )

• increased segmental glomerulosclerosis in response to doxorubicin-induced podocyte injury

homeostasis/metabolism

albuminuria ( J:333727 )

• increased urinary albumin-creatinine ratio in response to doxorubicin-induced podocyte injury

increased susceptibility to injury ( J:333727 )

• following injection of adriamycin (doxorubicin) at 6 weeks of age to induce podocyte injury, 14-week-old mice exhibit histologic lesions and a significantly higher urinary albumin-creatinine ratio and glomerulosclerosis score than similarly treated control mice

cellular

increased mesangial cell number ( J:333727 )

• increased mesangial cell proliferation in response to doxorubicin-induced podocyte injury

Genotype
MGI:7657843

cn29

• Allelic Composition: Kctd1^{tm1c(EUCOMM)Wtsi}/Kctd1^{tm1c(EUCOMM)Wtsi}; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * SJL

renal/urinary system

renal/urinary system phenotype ( J:344153 )

N • at 2-4 months of age, mice exhibit normal kidney morphology with no alterations in blood urea nitrogen (BUN) levels relative to controls, indicating normal kidney function

Genotype
MGI:7657844

cn30

• Allelic Composition: Kctd15^{tm1c(EUCOMM)Wtsi}/Kctd15^{tm1c(EUCOMM)Wtsi}; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * SJL
• Cell Lines: EPD0177_1_E09

renal/urinary system

renal/urinary system phenotype ( J:344153 )

N • at 2-4 months of age, mice exhibit normal kidney morphology with no alterations in blood urea nitrogen (BUN) levels relative to controls, indicating normal kidney function

Genotype
MGI:3715142

cn31

• Allelic Composition: Ldb1^tm1Witz/Ldb1^tm1Witz; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: C57BL/6 * SJL

mortality/aging

premature death ( J:122505 )

• most animals die by 4 weeks of age, with a very few surviving 3 months

renal/urinary system

abnormal glomerular capillary endothelium morphology ( J:122505 )

• by 19 days of age, endothelial cells have lifted off the glomerular basement membrane

absent glomerular endothelium fenestra ( J:122505 )

• by 19 days of age, endothelial fenestrations are largely absent

albuminuria ( J:122505 )

• at 19 days, pronounced proteinuria is observed

abnormal podocyte foot process morphology ( J:122505 )

• gradual loss of foot processes is seen

podocyte foot process effacement ( J:122505 )

• occasional foot process effacement can be seen at 5 days and becomes widespread by 19 days of age

abnormal renal glomerulus basement membrane morphology ( J:122505 )

• a split glomerular basement membrane is observed at 5 days

renal glomerular synechia ( J:122505 )

• by 19 days of age, adhesions to Bowman's capsule are observed

renal glomerulus atrophy ( J:122505 )

• at 19 days of age, glomeruli appear atrophied

dilated renal tubule ( J:122505 )

• dilated tubules containing proteinaceous material are seen at 19 days

renal cast ( J:122505 )

• frequent dilated tubular profiles filled with an eosinophilic material are seen at 19 days

homeostasis/metabolism

albuminuria ( J:122505 )

• at 19 days, pronounced proteinuria is observed

cardiovascular system

abnormal glomerular capillary endothelium morphology ( J:122505 )

• by 19 days of age, endothelial cells have lifted off the glomerular basement membrane

absent glomerular endothelium fenestra ( J:122505 )

• by 19 days of age, endothelial fenestrations are largely absent

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nail-patella syndrome		DOID:9467	OMIM:161200	J:122505

Genotype
MGI:3691146

cn32

• Allelic Composition: Itga3^tm1Son/Itga3^tm1Son; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: Not Specified

Glomerular basement membrane abnormalities and foot process effacement in kidneys of mildly affected Cd151^tm1Nki/Cd151^tm1Nki and Itga3^tm1Son/Itga3^tm1Son Tg(NPHS2-cre)295Lbh/0 mice

renal/urinary system

increased urine protein level ( J:114988 )

• exhibit massive proteinuria starting within the first week of age

albuminuria ( J:114988 )

podocyte foot process effacement ( J:114988 )

• complete effacement of podocyte foot processes in newborns

abnormal renal glomerulus basement membrane morphology ( J:114988 )

• glomerular basement membrane (GBM) is disorganized

• 6 week old mutants show widespread lamination and protrusions of the GBM

increased renal glomerulus basement membrane thickness ( J:114988 )

• abnormally thickened GBM with protrusions throughout the glomerulus

glomerulosclerosis ( J:114988 )

• kidneys contain partially sclerosed glomeruli

dilated proximal convoluted tubule ( J:114988 )

• dilated proximal tubules contain prominent protein casts

renal cast ( J:114988 )

• dilated proximal tubules contain prominent protein casts

pale kidney ( J:114988 )

• milky, discolored kidneys

homeostasis/metabolism

edema ( J:114988 )

• develop abdominal edema at 5-6 weeks of age

increased urine protein level ( J:114988 )

• exhibit massive proteinuria starting within the first week of age

albuminuria ( J:114988 )

Genotype
MGI:6401290

tg33

• Allelic Composition: Tg(NPHS2-cre)295Lbh/Tg(NPHS2-cre)295Lbh
• Genetic Background: 129S6.Cg-Tg(NPHS2-cre)295Lbh/BroJ

renal/urinary system

podocyte foot process effacement ( J:285845 )

increased renal glomerulus basement membrane thickness ( J:285845 )

• at 24 weeks of age

Genotype
MGI:6401289

tg34

• Allelic Composition: Tg(NPHS2-cre)295Lbh/0
• Genetic Background: 129S6.Cg-Tg(NPHS2-cre)295Lbh/BroJ

renal/urinary system

podocyte foot process effacement ( J:285845 )

increased renal glomerulus basement membrane thickness ( J:285845 )

• at 24 weeks of age