Phenotypes associated with this allele

• Allele Symbol: Tg(Nphs1-cre)33Mska
• Allele Name: transgene insertion 33, Taiji Matsusaka
• Allele ID: MGI:3762483
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^+ Tg(Nphs1-cre)33Mska/0 Tg(Nphs1-IL2RA)18Mska/0	involves: 129S4/SvJaeSor * C57BL/6 * C57BL/6N * DBA/2	MGI:3762559
cn2	Prkci^tm1Kido/Prkci^tm1.1Kido Tg(Nphs1-cre)33Mska/0	involves: C57BL/6 * C57BL/6N * DBA/2	MGI:5295616
cn3	Tjp1^tm1.1Whun/Tjp1^tm1.1Whun Tg(Nphs1-cre)33Mska/0	involves: C57BL/6 * C57BL/6N * DBA/2	MGI:5770415

Genotype
MGI:3762559

cn1

• Allelic Composition: Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor⁺; Tg(Nphs1-cre)33Mska/0; Tg(Nphs1-IL2RA)18Mska/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * C57BL/6N * DBA/2

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

renal/urinary system

increased kidney cell proliferation ( J:126591 )

• proliferation of parietal epithelial cells, not podocytes, is observed; proliferating cells are lacZ-negative, whereas podocytes express beta-galactosidase

abnormal glomerular capsule parietal layer morphology ( J:126591 )

• vacuolar degeneration of parietal epithelial cells is observed after LMB2 treatment

• proliferation of parietal epithelial cells, not podocytes, is also seen; proliferating cells are lacZ-negative, whereas podocytes express beta-galactosidase

abnormal podocyte morphology ( J:126591 )

• vacuolar degeneration of podocytes is observed after LMB2 treatment; podocytes are identified by lacZ staining

• podocytes are lost temporally after LMB2 treatment, correlating with progression of sclerosis

abnormal renal glomerulus morphology ( J:126591 )

• hyalinosis is seen after LMB2 treatment

mesangiolysis ( J:126591 )

• mesangiolysis is seen after LMB2 treatment

glomerulosclerosis ( J:126591 )

• after treatment with the immunotoxin LMB2, transgenic animal rapidly develop glomerulosclerosis

• 18%, 23%, and 60% of glomeruli show segmental or global sclerosis at 10, 14 or 21 days after treatment, respectively

cellular

increased kidney cell proliferation ( J:126591 )

• proliferation of parietal epithelial cells, not podocytes, is observed; proliferating cells are lacZ-negative, whereas podocytes express beta-galactosidase

Genotype
MGI:5295616

cn2

• Allelic Composition: Prkci^tm1Kido/Prkci^tm1.1Kido; Tg(Nphs1-cre)33Mska/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * DBA/2

Focal segmental glomerulosclerosis in Prkci^tm1Kido/Prkci^tm1.1Kido Tg(Nphs1-cre)33Mska/0 mice

mortality/aging

premature death ( J:144995 )

• mice exhibit a reduced lifespan with a median age of death of 6 weeks

growth/size/body

postnatal growth retardation ( J:144995 )

• mice exhibit growth retardation by 4 weeks of age

renal/urinary system

detached podocyte ( J:144995 )

• partial detachment of podocytes with an irregular pattern of nephrin staining is seen at P10

increased urine protein level ( J:144995 )

• mice exhibit massive proteinuria at P0 and throughout their lives

• however, kidneys appear grossly normal at P0

abnormal podocyte morphology ( J:144995 )

fused podocyte foot processes ( J:144995 )

• at P10, irregular adhesions between foot processes are observed

podocyte foot process effacement ( J:144995 )

• at P10, effacement of foot processes is observed

• however, fine foot processes are noted at P0

abnormal podocyte polarity ( J:144995 )

• at P7-P10, the apico-basal cell polarity of podocytes is disturbed

• at P7, podocalyxin loses its apically restricted localization, whereas ZO-1 localizes at the irregular cell-cell junctions of podocytes

abnormal podocyte slit junction morphology ( J:144995 )

• at P10, irregular adhesions between foot processes do not form tight junctions

abnormal podocyte slit diaphragm morphology ( J:144995 )

• at P7-P10, apically dislocated slit diaphragms are observed

• however, normal slit diaphragms are noted at P0

decreased podocyte number ( J:144995 )

• loss of podocytes is noted by P21

abnormal renal glomerulus morphology ( J:144995 )

• at P10, glomeruli display partial detachment of podocytes, occasional adhesion of glomeruli to Bowman's capsules, mesangial expansion, dilated capillaries, and an irregular pattern of nephrin staining

dilated glomerular capillary ( J:144995 )

• at P10, glomerular capillaries are dilated

expanded mesangial matrix ( J:144995 )

• at P10

glomerulosclerosis ( J:144995 )

• by P21, glomeruli exhibit advanced segmental to global sclerotic lesions, consistent with severe renal dysfunction

renal glomerular synechia ( J:144995 )

• at P10, occasional adhesion of glomeruli to Bowman's capsules is observed

abnormal proximal convoluted tubule morphology ( J:144995 )

• at P0, PAS staining indicates occasional hyaline droplets, representing reabsorbed urinary protein, in proximal renal tubules

renal cast ( J:144995 )

• at P0, PAS staining indicates occasional hyaline droplets, representing reabsorbed urinary protein, in proximal renal tubules

homeostasis/metabolism

increased circulating creatinine level ( J:144995 )

• mice display a significantly increased serum creatinine level by 3 weeks of age

increased blood urea nitrogen level ( J:144995 )

• mice display a significantly increased blood urea nitrogen level by 3 weeks of age

increased urine protein level ( J:144995 )

• mice exhibit massive proteinuria at P0 and throughout their lives

• however, kidneys appear grossly normal at P0

cardiovascular system

dilated glomerular capillary ( J:144995 )

• at P10, glomerular capillaries are dilated

cellular

detached podocyte ( J:144995 )

• partial detachment of podocytes with an irregular pattern of nephrin staining is seen at P10

Genotype
MGI:5770415

cn3

• Allelic Composition: Tjp1^tm1.1Whun/Tjp1^tm1.1Whun; Tg(Nphs1-cre)33Mska/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * DBA/2

Growth retardation and severe glomerulosclerosis in Tjp1^tm1.1Whun/Tjp1^tm1.1WhunTg(Nphs1-cre)33Mska/0 mice

growth/size/body

postnatal growth retardation ( J:226210 )

• significant growth retardation at 6 weeks of age

renal/urinary system

detached podocyte ( J:226210 )

• impaired adhesion of the podocyte foot processes to the GBM at 2 weeks but not at 1 week of age

increased urine protein level ( J:226210 )

• significant proteinuria at 2 weeks of age

• massive proteinuria at 6 weeks of age

• albumin and higher molecular weight proteins detected in urine at P0

albuminuria ( J:226210 )

• albumin is detected in the urine at P0

abnormal kidney morphology ( J:226210 )

• disordered tissue architecture at 6 weeks of age, as shown by PAS staining

abnormal podocyte foot process morphology ( J:226210 )

• severe disorganization and destruction of the foot processes at 6 weeks of age

• disorganized interdigitation at 1 week of age

• loss of interdigitation at 2 weeks of age

• foot processes are located close together in maturing podocytes at P0

fused podocyte foot processes ( J:226210 )

• aberrant contacts between the foot processes at 2 weeks of age

podocyte foot process effacement ( J:226210 )

• global foot process effacement at 2 weeks of age

abnormal podocyte slit diaphragm morphology ( J:226210 )

• abnormal distribution of the slit diaphragm components at 1 week and 2 weeks of age

• absence of normal slit diaphragms in maturing podocytes in P0

absent podocyte slit diaphragm ( J:226210 )

• loss of the slit diaphragm at 2 weeks of age

increased renal glomerulus basement membrane thickness ( J:226210 )

• however, GBM organization is largely normal at 2 weeks of age

• abnormally thickened, tortuous GBM at 6 weeks of age

abnormal glomerular filtration barrier morphology ( J:226210 )

• impaired formation and maintenance of the podocyte filtration barrier

glomerulosclerosis ( J:226210 )

• severe glomerulosclerosis at 4 weeks of age, with milder but obvious glomerular defects at 2 weeks of age

• global sclerosis (>90%) with extensive deposits of basement membrane components, as shown by Jones silver and Massons trichrome staining, at 6 weeks of age

abnormal kidney pelvis morphology ( J:226210 )

• enlarged renal pelvis at 6 weeks but not at 2 weeks of age

kidney papillary atrophy ( J:226210 )

• atrophic renal papilla at 6 weeks but not at 2 weeks of age

dilated renal tubule ( J:226210 )

• dilated renal tubules at 4 and 6 weeks of age

renal cast ( J:226210 )

• proteinaceous casts within dilated renal tubules at 4 weeks of age

granular kidney ( J:226210 )

• kidneys have a more granular surface at 6 weeks of age

pale kidney ( J:226210 )

• pale kidneys at 6 weeks of age

homeostasis/metabolism

increased urine protein level ( J:226210 )

• significant proteinuria at 2 weeks of age

• massive proteinuria at 6 weeks of age

• albumin and higher molecular weight proteins detected in urine at P0

albuminuria ( J:226210 )

• albumin is detected in the urine at P0

cellular

detached podocyte ( J:226210 )

• impaired adhesion of the podocyte foot processes to the GBM at 2 weeks but not at 1 week of age