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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(NPHS2-cre)295Lbh
transgene insertion 295, Lawrence B Holzman
MGI:2450359
Summary 31 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Jamltm1Fnyi/Jamltm1Fnyi
Tg(NPHS2-cre)295Lbh/0
B6.Cg-Jamltm1Fnyi Tg(NPHS2-cre)295Lbh MGI:6506861
cn2
Jamltm1Fnyi/Jaml+
Leprdb/Leprdb
Tg(NPHS2-cre)295Lbh/0
B6.Cg-Leprdb Jamltm1Fnyi Tg(NPHS2-cre)295Lbh MGI:6506863
cn3
Jamltm1Fnyi/Jamltm1Fnyi
Leprdb/Leprdb
Tg(NPHS2-cre)295Lbh/0
B6.Cg-Leprdb Jamltm1Fnyi Tg(NPHS2-cre)295Lbh MGI:6506864
cn4
Myh9tm1.1Gac/Myh9tm1.1Gac
Tg(NPHS2-cre)295Lbh/0
involves: 129 * C57BL/6 * SJL MGI:5432397
cn5
Cfl1tm1.1Wit/Cfl1tm1.1Wit
Tg(NPHS2-cre)295Lbh/0
involves: 129 * C57BL/6 * SJL MGI:5432555
cn6
Cmastm1.1Bwei/Cmastm1.1Bwei
Tg(NPHS2-cre)295Lbh/0
involves: 129P2/OlaHsd * C57BL/6 * SJL MGI:6402523
cn7
Prkcitm1Rfar/Prkcitm1Rfar
Tg(NPHS2-cre)295Lbh/0
involves: 129P2/OlaHsd * C57BL/6 * SJL MGI:5446036
cn8
Pdss2tm1Dalg/Pdss2tm1Dalg
Tg(NPHS2-cre)295Lbh/?
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:3805706
cn9
Agrntm1Rwb/Agrntm1Rwb
Tg(NPHS2-cre)295Lbh/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:3716770
cn10
Lama5tm2Jhm/Lama5tm1Jhm
Tg(NPHS2-cre)295Lbh/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL MGI:5432560
cn11
Lama5tm2Jhm/Lama5tm2Jhm
Tg(NPHS2-cre)295Lbh/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL MGI:5432561
cn12
Cd2bp2tm1.1Tbh/Cd2bp2tm1.1Tbh
Tg(NPHS2-cre)295Lbh/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N * SJL MGI:6392043
cn13
Ilktm1Star/Ilktm1Star
Tg(NPHS2-cre)295Lbh/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL MGI:5432357
cn14
Scribtm1.1Geno/Scribtm1.1Geno
Tg(NPHS2-cre)295Lbh/0
involves: 129S1/SvImJ * C57BL/6 * SJL MGI:5449169
cn15
Vhltm1Jae/Vhltm1Jae
Tg(NPHS2-cre)295Lbh/?
involves: 129S4/SvJae * C57BL/6 * SJL MGI:5432351
cn16
Tcf3tm4Zhu/Tcf3tm4Zhu
Tg(NPHS2-cre)295Lbh/0
involves: 129S4/SvJaeSor * C57BL/6 * SJL MGI:3715143
cn17
Myo1etm1Flv/Myo1etm1Flv
Tg(NPHS2-cre)295Lbh/0
involves: 129S6/SvEvTac * C57BL/6 * SJL MGI:5445941
cn18
Ano1tm2Jrr/Ano1tm2Jrr
Tg(NPHS2-cre)295Lbh/0
involves: 129S6/SvEvTac * C57BL/6 * SJL MGI:5569649
cn19
Myo1etm1Flv/Myo1etm1.1Flv
Tg(NPHS2-cre)295Lbh/0
involves: 129S6/SvEvTac * C57BL/6 * SJL MGI:5445942
cn20
Lmx1btm4.1Rjo/Lmx1btm4.1Rjo
Tg(NPHS2-cre)295Lbh/0
involves: 129S7/SvEvBrd * C57BL/6 * SJL MGI:3715141
cn21
Fat1tm1.1Nsib/Fat1+
Tg(NPHS2-cre)295Lbh/0
involves: 129/Sv * 129S4/SvJaeSor * C57BL/6 * C57BL/6J * SJL MGI:6160428
cn22
Fat1tm1.1Nsib/Fat1tm1.1Nsib
Tg(NPHS2-cre)295Lbh/0
involves: 129/Sv * 129S4/SvJaeSor * C57BL/6 * C57BL/6J * SJL MGI:6160427
cn23
Rhoatm1Jrel/Rhoatm1Jrel
Rhpn1tm1Ktry/Rhpn1tm1Ktry
Tg(NPHS2-cre)295Lbh/0
involves: 129X1/SvJ * C57BL/6 * SJL MGI:6360618
cn24
Itgb1tm1Efu/Itgb1tm1Efu
Tg(NPHS2-cre)295Lbh/0
involves: 129X1/SvJ * C57BL/6 * SJL MGI:5142307
cn25
Coq8btm1c(EUCOMM)Hmgu/Coq8btm1c(EUCOMM)Hmgu
Tg(NPHS2-cre)295Lbh/0
involves: C3H * C57BL/6 * C57BL/6N * SJL MGI:6455521
cn26
Coq6tm1c(EUCOMM)Hmgu/Coq6tm1c(EUCOMM)Hmgu
Tg(NPHS2-cre)295Lbh/0
involves: C57BL/6 * C57BL/6N * SJL MGI:6459750
cn27
Atp6ap2tm1.1Ics/Y
Tg(NPHS2-cre)295Lbh/0
involves: C57BL/6 * C57BL/6N * SJL MGI:5779963
cn28
Ldb1tm1Witz/Ldb1tm1Witz
Tg(NPHS2-cre)295Lbh/0
involves: C57BL/6 * SJL MGI:3715142
cn29
Itga3tm1Son/Itga3tm1Son
Tg(NPHS2-cre)295Lbh/0
Not Specified MGI:3691146
tg30
Tg(NPHS2-cre)295Lbh/Tg(NPHS2-cre)295Lbh 129S6.Cg-Tg(NPHS2-cre)295Lbh/BroJ MGI:6401290
tg31
Tg(NPHS2-cre)295Lbh/0 129S6.Cg-Tg(NPHS2-cre)295Lbh/BroJ MGI:6401289


Genotype
MGI:6506861
cn1
Allelic
Composition
Jamltm1Fnyi/Jamltm1Fnyi
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
B6.Cg-Jamltm1Fnyi Tg(NPHS2-cre)295Lbh
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Jamltm1Fnyi mutation (0 available); any Jaml mutation (19 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• in mice treated with streptozocin and fed a high-fat diet to induce diabetes to a lesser extent than in wild-type mice
• mice treated with streptozocin and fed a high-fat diet to induce diabetes fail to compared with similarly treated mice
• mice treated with adriamycin to induce nephropathy exhibit lower urinary albumin excretion compared with similarly treated wild-type mice
• in mice treated with streptozocin and fed a high-fat diet to induce diabetes to a lesser extent than in wild-type mice
• mice treated with adriamycin to induce nephropathy exhibit less glomerulosclerosis compared with similarly treated wild-type mice
• 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
• mice treated with streptozocin and fed a high-fat diet to induce diabetes fail to compared with similarly treated mice
• mice treated with adriamycin to induce nephropathy exhibit lower urinary albumin excretion compared with similarly treated wild-type mice
• 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
• 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:6506863
cn2
Allelic
Composition
Jamltm1Fnyi/Jaml+
Leprdb/Leprdb
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
B6.Cg-Leprdb Jamltm1Fnyi Tg(NPHS2-cre)295Lbh
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Jamltm1Fnyi mutation (0 available); any Jaml mutation (19 available)
Leprdb mutation (17 available); any Lepr mutation (93 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• intermediate but not as severe as in mice with wild-type Jaml
• podocyte injury that is as severe as in mice with wild-type Jaml
• not as severe as in mice with wild-type Jaml

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




Genotype
MGI:6506864
cn3
Allelic
Composition
Jamltm1Fnyi/Jamltm1Fnyi
Leprdb/Leprdb
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
B6.Cg-Leprdb Jamltm1Fnyi Tg(NPHS2-cre)295Lbh
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Jamltm1Fnyi mutation (0 available); any Jaml mutation (19 available)
Leprdb mutation (17 available); any Lepr mutation (93 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• not as severe as in mice with wild-type Jaml
• podocyte injury that is as severe as in mice with wild-type Jaml
• not as severe as in mice with wild-type Jaml
• not as severe as in mice with wild-type Jaml

homeostasis/metabolism
• not as severe as in mice with wild-type Jaml




Genotype
MGI:5432397
cn4
Allelic
Composition
Myh9tm1.1Gac/Myh9tm1.1Gac
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129 * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Myh9tm1.1Gac mutation (3 available); any Myh9 mutation (226 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
N
• surprisingly, mice are viable and do not develop overt chronic kidney disease up to 9 months of age
• no excessive proteinuria at 1-9 months of age relative to control mice
• normal urine albumin/creatinine ratios at 3-9 months of age relative to control mice
• at 3, 4, and 6 weeks after adriamycin injection, mice develop significantly more albuminuria than similarly-treated control mice
• after adriamycin injection, mice exhibit patches of foot process fusion, unlike similarly-treated control mice
• after adriamycin injection, mice exhibit patches of severe foot process effacement, unlike similarly-treated control mice
• after adriamycin injection, mice exhibit evidence of pseudovillous transformation, unlike similarly-treated control mice
• after adriamycin injection, mice exhibit thickening of the basement membrane in some glomerular loops, unlike similarly-treated control mice
• 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
• at 6 weeks after adriamycin injection, mice exhibit numerous proteinaceous casts, unlike similarly-treated control mice

homeostasis/metabolism
N
• no excessive proteinuria at 1-9 months of age relative to control mice
• normal urine albumin/creatinine ratios at 3-9 months of age relative to control mice
• normal serum creatinine and BUN levels at 9 months of age relative to control mice
• at 3, 4, and 6 weeks after adriamycin injection, mice develop significantly more albuminuria than similarly-treated control mice
• 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
N
• normal body weight at 9 months of age relative to control mice

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




Genotype
MGI:5432555
cn5
Allelic
Composition
Cfl1tm1.1Wit/Cfl1tm1.1Wit
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129 * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cfl1tm1.1Wit mutation (0 available); any Cfl1 mutation (23 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice exhibit a reduced life span with a median age at death of 9 months

homeostasis/metabolism
• significant increase in serum creatinine levels at 6 months of age, indicating renal dysfunction
• large ascites detected at 9 months of age
• mice develop persistent proteinuria by 3 months of age
• rate of proteinuria increases modestly until 6 months and accelerates more rapidly thereafter
• 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
N
• mice exhibit no evidence of glomerular or interstitial scarring, even at 9 months of age
• mice develop persistent proteinuria by 3 months of age
• rate of proteinuria increases modestly until 6 months and accelerates more rapidly thereafter
• 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
• 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
• mice exhibit a scruffed appearance at 9 months of age




Genotype
MGI:6402523
cn6
Allelic
Composition
Cmastm1.1Bwei/Cmastm1.1Bwei
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cmastm1.1Bwei mutation (0 available); any Cmas mutation (15 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• dilatation and narrowing at P42

growth/size/body
• starting at P28
• starting at P28

homeostasis/metabolism
• progressive, starting around P28

immune system
• eosinophilic material in some proximal and distal tubules at P28

mortality/aging
• between postnatal weeks 6 and 8

renal/urinary system
• dilatation and narrowing at P42
• progressive, starting around P28
• eosinophilic material in some proximal and distal tubules at P28
• resulting in podocyte fusion, complete loss of slit diaphragm and microvillous transformation at P42
• with reduction in mature slit diaphragm at P28
• 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
• 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
• of glomerular tufts to Bowmans capsule with dilation of both at P42
• increased collagen deposition at P42
• reduced glomerular filtration rate at P28

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
Prkcitm1Rfar/Prkcitm1Rfar
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prkcitm1Rfar mutation (0 available); any Prkci mutation (69 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• at ~4 weeks of age, mice exhibit significant growth retardation relative to controls

renal/urinary system
• at ~4 weeks of age, mice exhibit significant proteinuria relative to controls
• 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
• at ~4 weeks of age, foot processes appear globally effaced
• at ~4 weeks of age, severe junctional abnormalities are observed
• at ~4 weeks of age, foot processes often display significant slit diaphragm displacement
• at ~4 weeks of age, mice develop segmental glomerulosclerosis
• at ~4 weeks of age, mice exhibit renal tubule dilation
• at ~4 weeks of age, mice exhibit proteinuric casts in the tubule system
• mice develop nephrotic syndrome and die of renal failure

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




Genotype
MGI:3805706
cn8
Allelic
Composition
Pdss2tm1Dalg/Pdss2tm1Dalg
Tg(NPHS2-cre)295Lbh/?
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pdss2tm1Dalg mutation (0 available); any Pdss2 mutation (24 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• histological evidence of nephritis
• extensive interstitial infiltration

homeostasis/metabolism
• elevated plasma cholesterol

immune system
• histological evidence of nephritis




Genotype
MGI:3716770
cn9
Allelic
Composition
Agrntm1Rwb/Agrntm1Rwb
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Agrntm1Rwb mutation (1 available); any Agrn mutation (59 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
N
• when compared to normal controls, no pathological changes are detected until at least 8 months of age
• 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
• at ~4 months of age, glomerular basement membrane (GBM) abnormalities including focal thickening and epithelial protrusions of GBM material are observed in mutants
• focal thickening of the GBM is noted at ~4 months of age




Genotype
MGI:5432560
cn10
Allelic
Composition
Lama5tm2Jhm/Lama5tm1Jhm
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lama5tm1Jhm mutation (0 available); any Lama5 mutation (104 available)
Lama5tm2Jhm mutation (0 available); any Lama5 mutation (104 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• animals show mild proteinuria early in life (3 weeks), and progress to the nephrotic range of disease
• observed with age
• yellowing of the kidneys is observed with age
• increased thickness, a moth-eated appearance and irregular contours with frequent subepithelial outpocketings are observed at late disease stages
• observed at late stages of disease
• observed at late stages of disease

homeostasis/metabolism
• mice become edematous with age
• animals show mild proteinuria early in life (3 weeks), and progress to the nephrotic range of disease
• observed with age

immune system




Genotype
MGI:5432561
cn11
Allelic
Composition
Lama5tm2Jhm/Lama5tm2Jhm
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lama5tm2Jhm mutation (0 available); any Lama5 mutation (104 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
Cd2bp2tm1.1Tbh/Cd2bp2tm1.1Tbh
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd2bp2tm1.1Tbh mutation (0 available); any Cd2bp2 mutation (22 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• premature death at 15 to 30 weeks of age

renal/urinary system
• severe starting at 2 months of age
• however, blood capillaries and fenestration of the endothelium are unchanged
• in the renal tubules

growth/size/body
• starting at 10 weeks of age

homeostasis/metabolism
• severe starting at 2 months of age




Genotype
MGI:5432357
cn13
Allelic
Composition
Ilktm1Star/Ilktm1Star
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ilktm1Star mutation (1 available); any Ilk mutation (16 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• only a few mice survive beyond 6 months of age
• 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
• significantly decreased body weight first noted at 10 weeks of age

renal/urinary system
• 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)
• marked apoptosis in the tubulointerstitial area of the kidney at 10 weeks of age, unlike in control mice
• 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
• 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)
• 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 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)
• at 16 weeks of age, nephrotic end-stage kidneys appear yellow and display a rough surface
• 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 foot processes are noted at 10 weeks of age
• 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)
• 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)
• a ~70% reduction in the number of podocytes per glomerulus is first seen at 10 weeks of age
• 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)
• 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)
• 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)
• primary glomerular lesions first seen at 10 weeks of age
• distorted capillaries at 4 and 12 weeks of age
• 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)
• 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)
• crescent formation at 12 weeks of age
• tuft adhesions to Bowman's capsule at 12 weeks of age
• enlarged glomerular size at 10 weeks of age
• at 12 and 16 weeks of age (J:129244)
• mild interstitial fibrosis at 10 weeks of age (J:129286)
• at 12 weeks of age
• extensive tubular dilation distended by proteinaceous fluid and cellular debris at 10 weeks of age
• progressive filtration barrier failure
• mice die of kidney failure (J:129244)
• age-dependent deterioration of kidney function (J:129286)

homeostasis/metabolism
• significantly increased serum creatinine levels at 10 but not at 4 weeks of age
• 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)
• 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 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
• distorted capillaries at 4 and 12 weeks of age

cellular
• 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)
• marked apoptosis in the tubulointerstitial area of the kidney at 10 weeks of age, unlike in control mice
• 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
Scribtm1.1Geno/Scribtm1.1Geno
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S1/SvImJ * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Scribtm1.1Geno mutation (0 available); any Scrib mutation (34 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
N
• no abnormalities in renal glomerular structure or function




Genotype
MGI:5432351
cn15
Allelic
Composition
Vhltm1Jae/Vhltm1Jae
Tg(NPHS2-cre)295Lbh/?
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(NPHS2-cre)295Lbh mutation (3 available)
Vhltm1Jae mutation (2 available); any Vhl mutation (14 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
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
• no changes in peritubular microvessels or larger arterioles and veins are observed
• dilated glomerular capillary lumen noted in mice with severe albuminuria as early as 4 weeks of age
• 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 medullary collecting ducts noted in nonproteinuric mice at 4 weeks of age
• podocyte foot process broadening noted in all nonproteinuric mice at 4 weeks of age
• significant decrease in podocyte number noted in both proteinuric and nonproteinuric mice at 4 weeks of age, as shown WT1 staining
• incompletely fused or fragmented GBM noted on the subendothelial side of the capillary loop in nonproteinuric mice at 4 weeks of age
• 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
• mesangial hypercellularity noted in mice with severe albuminuria at 4 weeks of age
• 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 crescents noted in mice with severe albuminuria at 4 weeks of age
• severely fibrotic glomeruli noted in mice with massive albuminuria at 25 weeks of age
• noted in mice with severe albuminuria at 25 weeks of age
• 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
• 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
• end-stage renal failure observed in mice with the highest levels of albuminuria

homeostasis/metabolism
• 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 noted in mice with the highest levels of albuminuria
• 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
• wasting noted in mice with the highest levels of albuminuria

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




Genotype
MGI:3715143
cn16
Allelic
Composition
Tcf3tm4Zhu/Tcf3tm4Zhu
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S4/SvJaeSor * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tcf3tm4Zhu mutation (2 available); any Tcf3 mutation (31 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• 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
Myo1etm1Flv/Myo1etm1Flv
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Myo1etm1Flv mutation (1 available); any Myo1e mutation (75 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• 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
• by 4 months of age, the average number of foot processes per unit length of the basement membrane is lower than that in controls
• 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
• by 4 months of age, the overall outline of the GBM appears jagged and uneven, unlike in control mice
• 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
• at 8 months of age, mice exhibit some sclerotic glomeruli, unlike control mice
• however, no glomerulosclerosis is seen at 4 months
• 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
• 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:5569649
cn18
Allelic
Composition
Ano1tm2Jrr/Ano1tm2Jrr
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ano1tm2Jrr mutation (0 available); any Ano1 mutation (35 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
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:5445942
cn19
Allelic
Composition
Myo1etm1Flv/Myo1etm1.1Flv
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Myo1etm1.1Flv mutation (1 available); any Myo1e mutation (75 available)
Myo1etm1Flv mutation (1 available); any Myo1e mutation (75 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• 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 Myo1etm1.1Flv homozygotes
• at 7 months of age, mice exhibit some sclerotic glomeruli, unlike control mice
• at 7 months of age, mice exhibit a few proteinaceous casts, unlike control mice

homeostasis/metabolism
• 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 Myo1etm1.1Flv homozygotes




Genotype
MGI:3715141
cn20
Allelic
Composition
Lmx1btm4.1Rjo/Lmx1btm4.1Rjo
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129S7/SvEvBrd * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmx1btm4.1Rjo mutation (1 available); any Lmx1b mutation (13 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• most mice do not live past 14 days after birth

renal/urinary system
• severe within 5 days postnatal
• loss of podocyte foot processes is observed at 5 days, becoming more prominent by 11 days after birth
• foot process effacement is apparent by 11 days after birth
• loss of slit diaphragms between podocytes is observed by 11 days after birth
• thickening of the glomerular basement membrane is observed by 11 days after birth
• by 11 days after birth, kidneys develop a focal-segmental glomerulosclerosis
• adhesions between the glomerular tuft and Bowman's capsule are seen in kidneys at 11 days
• occasional dilated tubular profiles at 5 days of age
• occasional dilated tubules filled with an eosinophilic, probably proteinaceous material at 5 days of age
• mice die from renal failure

homeostasis/metabolism
• 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
Fat1tm1.1Nsib/Fat1+
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129/Sv * 129S4/SvJaeSor * C57BL/6 * C57BL/6J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fat1tm1.1Nsib mutation (0 available); any Fat1 mutation (137 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• mice develop a very mild albuminuria

renal/urinary system
• mice develop a very mild albuminuria
• mice show only mild mesangial expansion




Genotype
MGI:6160427
cn22
Allelic
Composition
Fat1tm1.1Nsib/Fat1tm1.1Nsib
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129/Sv * 129S4/SvJaeSor * C57BL/6 * C57BL/6J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fat1tm1.1Nsib mutation (0 available); any Fat1 mutation (137 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• adults develop progressive proteinuria with massive albuminuria at 40 months of age
• 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
• adults develop progressive proteinuria with massive albuminuria at 40 months of age
• massive albuminuria is seen at 40 months of age, about 60-fold higher than in controls
• however, serum albumin is not different
• adults show collapsed F-actin in podocytes
• cell junctions of effaced foot processes resemble tight junctions
• adults show widespread foot process effacement
• 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
• adults show microvillar transformation
• 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
Rhoatm1Jrel/Rhoatm1Jrel
Rhpn1tm1Ktry/Rhpn1tm1Ktry
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129X1/SvJ * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rhoatm1Jrel mutation (0 available); any Rhoa mutation (94 available)
Rhpn1tm1Ktry mutation (0 available); any Rhpn1 mutation (27 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• reduced body weight by 3 months of age

homeostasis/metabolism

renal/urinary system
• mice exhibit a more severe kidney injury than single Rhpn1 homozygotes
• complete podocyte effacement
• segmental and global focal segmental glomerulosclerosis
• protein casts




Genotype
MGI:5142307
cn24
Allelic
Composition
Itgb1tm1Efu/Itgb1tm1Efu
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: 129X1/SvJ * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Itgb1tm1Efu mutation (2 available); any Itgb1 mutation (42 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• mice become less physically active at 3 weeks of age

growth/size/body
• at 6 weeks of age, mice are smaller than control littermates

homeostasis/metabolism
• mice develop severe edema at 3 weeks of age
• mice develop severe proteinuria by 6 weeks of age
• albuminuria is already evident at P1
• marked albuminuria is noted at 6 weeks of age

renal/urinary system
• 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
• mice develop severe proteinuria by 6 weeks of age
• albuminuria is already evident at P1
• marked albuminuria is noted at 6 weeks of age
• mice develop end stage kidney disease with pathological changes in the glomeruli and tubulo-interstitium
• at 6 weeks of age, many Bowmans capsules are either empty or contain partially degenerated glomeruli
• foot process effacement is first noted at E15.5
• extensive foot process effacement is noted at P10 and progresses by P21
• 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
• 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
• by P21, mice exhibit degeneration of the capillary loops
• however, normal glomerular capillary morphogenesis is noted at E15.5 and at P1
• 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
• mesangium hypercellularity is observed by 3 weeks of age
• increased mesangial matrix with focal defects is noted at 3 weeks, indicating mesangial injury
• multiple cytoplasmic vacuoles are first noted in mesangial cells at P10
• by P21, mice exhibit degeneration of the mesangium with little glomerulosclerosis
• 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
• at 6 weeks of age, end stage kidneys are smaller than those of age-matched control mice
• 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
• extensive proteinaceous tubular casts are noted at 6 weeks of age
• at 6 weeks of age, end stage kidneys are paler than those of age-matched control mice

cardiovascular system
• by P21, mice exhibit degeneration of the capillary loops
• however, normal glomerular capillary morphogenesis is noted at E15.5 and at P1
• 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
• 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
Coq8btm1c(EUCOMM)Hmgu/Coq8btm1c(EUCOMM)Hmgu
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: C3H * C57BL/6 * C57BL/6N * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Coq8btm1c(EUCOMM)Hmgu mutation (0 available); any Coq8b mutation (24 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• from age 9 months

cellular
• in glomerular podocytes as mice age 10 months
• in glomerular podocytes as mice age 10 months

homeostasis/metabolism
• from age 7 months
• increase in creatinine-albumin ratio from age 5 months
• from age 5 months
• increase in creatinine-albumin ratio from age 5 months
• increase in creatinine-albumin ratio from age 5 months

integument
• seedy fur from age 9 months

mortality/aging
• from age 9 months

renal/urinary system
• at age 10 months
• significantly reduced number of filtration-slit units per micrometer of basement membrane at age 10 months
• global and focal segmental glomerulosclerosis at age 10 months
• at age 10 months
• at age 10 months
• at age 10 months
• at age 10 months




Genotype
MGI:6459750
cn26
Allelic
Composition
Coq6tm1c(EUCOMM)Hmgu/Coq6tm1c(EUCOMM)Hmgu
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: C57BL/6 * C57BL/6N * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Coq6tm1c(EUCOMM)Hmgu mutation (0 available); any Coq6 mutation (24 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice become moribund at 10 months of age with advanced decline of kidney function
• 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 at >10 months of age
• treatment with 2,4-diHB ameliorates physical condition

integument
• scruffy fur at >10 months of age
• treatment with 2,4-diHB ameliorates physical condition

renal/urinary system
• obliteration of glomerular capillary lumens at 10 months of age
• males are more susceptible to proteinuria than females
• 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
• podocytes appear to contain abnormal mitochondria characterized by hyperproliferation and increased size at >10 months of age
• 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
• 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
• significant reduction in expression of podocyte-specific proteins and number of WT1+ podocytes at >10 months of age, suggesting depletion of podocytes
• significant thickening of the glomerulus basement membrane at 10, but not at 5, months of age
• 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
• significantly increased expression of fibrotic markers (alphaSMA, desmin, and collagen IV) in the glomeruli, typical of mesangial fibrosis, at >10 months of age
• extensive tubulointerstitial fibrosis at 10 months of age
• 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 at >10 months of age
• proteinaceous casts in dilated tubules at >10 months of age
• occasional protein casts in proximal tubules at 5 months of age
• kidneys appear pale upon necropsy at 10 months of age
• treatment with 2,4-diHB rescues macroscopic appearance of kidneys

homeostasis/metabolism
• males are more susceptible to proteinuria than females
• 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 number of mitochondria in podocytes at >10 months of age
• enlarged mitochondria in podocytes at >10 months of age
• increased size and number of mitochondria in podocytes at >10 months of age, indicating impaired mitochondrial function

cardiovascular system
• obliteration of glomerular capillary lumens at 10 months of age




Genotype
MGI:5779963
cn27
Allelic
Composition
Atp6ap2tm1.1Ics/Y
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: C57BL/6 * C57BL/6N * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Atp6ap2tm1.1Ics mutation (0 available); any Atp6ap2 mutation (12 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• between 2 and 3 weeks after birth

renal/urinary system
• at P2
• impaired vacuolar acidification with abnormal cytoskeleton organization and cell death
• massive protein enrichment
• protein casts in renal tubules

homeostasis/metabolism
• impaired in podocytes
• at P2

cellular
• impaired vacuolar acidification with abnormal cytoskeleton organization and cell death
• impaired in podocytes




Genotype
MGI:3715142
cn28
Allelic
Composition
Ldb1tm1Witz/Ldb1tm1Witz
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
involves: C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ldb1tm1Witz mutation (0 available); any Ldb1 mutation (31 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• most animals die by 4 weeks of age, with a very few surviving 3 months

renal/urinary system
• by 19 days of age, endothelial cells have lifted off the glomerular basement membrane
• by 19 days of age, endothelial fenestrations are largely absent
• at 19 days, pronounced proteinuria is observed
• gradual loss of foot processes is seen
• occasional foot process effacement can be seen at 5 days and becomes widespread by 19 days of age
• a split glomerular basement membrane is observed at 5 days
• by 19 days of age, adhesions to Bowman's capsule are observed
• at 19 days of age, glomeruli appear atrophied
• dilated tubules containing proteinaceous material are seen at 19 days
• frequent dilated tubular profiles filled with an eosinophilic material are seen at 19 days

homeostasis/metabolism
• at 19 days, pronounced proteinuria is observed

cardiovascular system
• by 19 days of age, endothelial cells have lifted off the glomerular basement membrane
• 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
cn29
Allelic
Composition
Itga3tm1Son/Itga3tm1Son
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
Not Specified
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Itga3tm1Son mutation (0 available); any Itga3 mutation (34 available)
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Glomerular basement membrane abnormalities and foot process effacement in kidneys of mildly affected Cd151tm1Nki/Cd151tm1Nki and Itga3tm1Son/Itga3tm1Son Tg(NPHS2-cre)295Lbh/0 mice

renal/urinary system
• exhibit massive proteinuria starting within the first week of age
• complete effacement of podocyte foot processes in newborns
• glomerular basement membrane (GBM) is disorganized
• 6 week old mutants show widespread lamination and protrusions of the GBM
• abnormally thickened GBM with protrusions throughout the glomerulus
• kidneys contain partially sclerosed glomeruli
• dilated proximal tubules contain prominent protein casts
• dilated proximal tubules contain prominent protein casts
• milky, discolored kidneys

homeostasis/metabolism
• develop abdominal edema at 5-6 weeks of age
• exhibit massive proteinuria starting within the first week of age




Genotype
MGI:6401290
tg30
Allelic
Composition
Tg(NPHS2-cre)295Lbh/Tg(NPHS2-cre)295Lbh
Genetic
Background
129S6.Cg-Tg(NPHS2-cre)295Lbh/BroJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system




Genotype
MGI:6401289
tg31
Allelic
Composition
Tg(NPHS2-cre)295Lbh/0
Genetic
Background
129S6.Cg-Tg(NPHS2-cre)295Lbh/BroJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(NPHS2-cre)295Lbh mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
01/24/2023
MGI 6.22
The Jackson Laboratory