Analysis Tools
normal phenotype
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• mice are viable and fertile and show no apparent growth or kidney related phenotypes
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Allele Symbol Allele Name Allele ID |
Tjp1tm1.1Whun targeted mutation 1.1, Walter Hunziker MGI:5749399 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable and fertile and show no apparent growth or kidney related phenotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 70-80% die by 4 weeks and all die by 6 weeks of age
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• mice start to die around 2 weeks of age
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• mean liver weight-to-body weight ratio is increased
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• marker analysis shows no, or rare, bile ducts in the periportal zone of the liver
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• liver is yellowish
• targeting of tight junctions and apical molecules is disrupted in the liver
• marker analysis indicates that liver zonation is perturbed
• however, no liver inflammation or fibrosis are seen
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• the lumina of the sinusoidal vessels are not clear
• marker analysis shows that sinusoidal vessels in the liver are injured
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• mean liver weight-to-body weight ratio is increased
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• the hepatic cords are not well-organized in the liver
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• normal bile canaliculi are hardly seen
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• individual hepatocytes appear slightly swollen with vacuole-like structures inside
• hepatocytes exhibit ectopic luminal structures around their basolateral domains
• hepatocyte cellular polarity is disrupted, with an unclear distinction between the apical and basolateral plasma membrane domains
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• mice show disruption of the hepatic barrier
• bile transport into bile canaliculi is diminished
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• mice show an increase in Ki-67+ hepatocytes, indicating increased hepatocyte proliferation
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• mice show increased levels of total bilirubin and direct bilirubin
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• mice show increased levels of alkaline phosphatase
• however, gamma-glutamyl transferase levels are normal
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• mice show increased levels of bile acids
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• the lumina of the sinusoidal vessels are not clear
• marker analysis shows that sinusoidal vessels in the liver are injured
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• mice show an increase in Ki-67+ hepatocytes, indicating increased hepatocyte proliferation
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• marker analysis shows no, or rare, bile ducts in the periportal zone of the liver
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| progressive familial intrahepatic cholestasis 4 | DOID:0070224 |
OMIM:615878 |
J:306936 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show normal total and direct bilirubin levels, bile acids, and alkaline phosphatase levels
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Growth retardation and severe glomerulosclerosis in Tjp1tm1.1Whun/Tjp1tm1.1WhunTg(Nphs1-cre)33Mska/0 mice
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• significant growth retardation at 6 weeks of age
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• impaired adhesion of the podocyte foot processes to the GBM at 2 weeks but not at 1 week of age
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• 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
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• albumin is detected in the urine at P0
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• disordered tissue architecture at 6 weeks of age, as shown by PAS staining
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• 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
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• aberrant contacts between the foot processes at 2 weeks of age
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• global foot process effacement at 2 weeks of age
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• 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
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• loss of the slit diaphragm at 2 weeks of age
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• abnormally thickened, tortuous GBM at 6 weeks of age
• however, GBM organization is largely normal at 2 weeks of age
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• impaired formation and maintenance of the podocyte filtration barrier
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• 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
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• enlarged renal pelvis at 6 weeks but not at 2 weeks of age
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• atrophic renal papilla at 6 weeks but not at 2 weeks of age
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• dilated renal tubules at 4 and 6 weeks of age
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• proteinaceous casts within dilated renal tubules at 4 weeks of age
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• kidneys have a more granular surface at 6 weeks of age
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• pale kidneys at 6 weeks of age
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• 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
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• albumin is detected in the urine at P0
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• impaired adhesion of the podocyte foot processes to the GBM at 2 weeks but not at 1 week of age
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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 04/30/2024 MGI 6.23 |
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