Phenotypes associated with this allele

• Allele Symbol: Tjp1^tm1.1Whun
• Allele Name: targeted mutation 1.1, Walter Hunziker
• Allele ID: MGI:5749399
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tjp1^tm1.1Whun/Tjp1^tm1.1Whun	involves: C57BL/6 * C57BL/6N	MGI:5770414
cn2	Tjp1^tm1.1Whun/Tjp1^tm1.1Whun Tjp2^tm2Whun/Tjp2^tm2Whun Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6N * C57BL/6NTac * DBA/2	MGI:6719082
cn3	Tjp1^tm1.1Whun/Tjp1^tm1.1Whun Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6N * C57BL/6NTac * DBA/2	MGI:6719088
cn4	Tjp1^tm1.1Whun/Tjp1^tm1.1Whun Tg(Nphs1-cre)33Mska/0	involves: C57BL/6 * C57BL/6N * DBA/2	MGI:5770415

Genotype
MGI:5770414

hm1

• Allelic Composition: Tjp1^tm1.1Whun/Tjp1^tm1.1Whun
• Genetic Background: involves: C57BL/6 * C57BL/6N

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

normal phenotype

no abnormal phenotype detected ( J:226210 )

• mice are viable and fertile and show no apparent growth or kidney related phenotypes

Genotype
MGI:6719082

cn2

• Allelic Composition: Tjp1^tm1.1Whun/Tjp1^tm1.1Whun; Tjp2^tm2Whun/Tjp2^tm2Whun; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6N * C57BL/6NTac * DBA/2

mortality/aging

premature death ( J:306936 )

• 70-80% die by 4 weeks and all die by 6 weeks of age

postnatal lethality, incomplete penetrance ( J:306936 )

• mice start to die around 2 weeks of age

growth/size/body

increased liver weight ( J:306936 )

• mean liver weight-to-body weight ratio is increased

liver/biliary system

abnormal hepatic duct morphology ( J:306936 )

• marker analysis shows no, or rare, bile ducts in the periportal zone of the liver

abnormal liver morphology ( J:306936 )

• 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

abnormal liver sinusoid morphology ( J:306936 )

• the lumina of the sinusoidal vessels are not clear

• marker analysis shows that sinusoidal vessels in the liver are injured

increased liver weight ( J:306936 )

• mean liver weight-to-body weight ratio is increased

abnormal hepatic cord morphology ( J:306936 )

• the hepatic cords are not well-organized in the liver

abnormal bile canaliculus morphology ( J:306936 )

• normal bile canaliculi are hardly seen

abnormal hepatocyte morphology ( J:306936 )

• 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

small liver ( J:306936 )

abnormal liver physiology ( J:306936 )

• mice show disruption of the hepatic barrier

• bile transport into bile canaliculi is diminished

increased hepatocyte proliferation ( J:306936 )

• mice show an increase in Ki-67+ hepatocytes, indicating increased hepatocyte proliferation

homeostasis/metabolism

increased circulating bilirubin level ( J:306936 )

• mice show increased levels of total bilirubin and direct bilirubin

increased circulating LDL cholesterol level ( J:306936 )

increased circulating alanine transaminase level ( J:306936 )

increased circulating alkaline phosphatase level ( J:306936 )

• mice show increased levels of alkaline phosphatase

• however, gamma-glutamyl transferase levels are normal

increased circulating aspartate transaminase level ( J:306936 )

increased bile salt level ( J:306936 )

• mice show increased levels of bile acids

cardiovascular system

abnormal liver sinusoid morphology ( J:306936 )

• the lumina of the sinusoidal vessels are not clear

• marker analysis shows that sinusoidal vessels in the liver are injured

cellular

increased hepatocyte proliferation ( J:306936 )

• mice show an increase in Ki-67+ hepatocytes, indicating increased hepatocyte proliferation

endocrine/exocrine glands

abnormal hepatic duct morphology ( J:306936 )

• marker analysis shows no, or rare, bile ducts in the periportal zone of the liver

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
progressive familial intrahepatic cholestasis 4		DOID:0070224	OMIM:615878	J:306936

Genotype
MGI:6719088

cn3

• Allelic Composition: Tjp1^tm1.1Whun/Tjp1^tm1.1Whun; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N * C57BL/6NTac * DBA/2

liver/biliary system

liver/biliary system phenotype ( J:306936 )

N • mice show normal total and direct bilirubin levels, bile acids, and alkaline phosphatase levels

Genotype
MGI:5770415

cn4

• 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 )

• abnormally thickened, tortuous GBM at 6 weeks of age

• however, GBM organization is largely normal at 2 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