cn1

Jag1^tm1Frad/Jag1^tm1Frad
Tg(Cdh5-cre)7Mlia/0
B6.Cg-Jag1^tm1Frad Tg(Cdh5-cre)7Mlia

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

mortality/aging

mortality/aging ( J:166890 )

N	• contrary to previous reports, viable mice are produced (J:166890)

cardiovascular system

abnormal pulmonary trunk morphology ( J:189213 )

• abnormal positioning of the aorta and pulmonary trunk

abnormal aorta morphology ( J:189213 )

• abnormal positioning of the aorta and pulmonary trunk

abnormal outflow tract development ( J:189213 )

abnormal heart morphology ( J:189213 )

abnormal coronary vessel morphology ( J:189213 )

• fragile and hemorrhaging in embryos and neonates

• thin and disorganized

overriding aortic valve ( J:189213 )

enlarged heart right atrium ( J:189213 )

• hypertrophy

ventricular septal defect ( J:189213 )

• incomplete at E14.5

abnormal heart valve morphology ( J:189213 )

• large and hyperplastic (myxomatous)

• neonates exhibit bulges near the valve annulus

• cartilage nodules and calcification in the annulus of adults

calcified aortic valve ( J:189213 )

pulmonary valve stenosis ( J:189213 )

thick heart valve cusps ( J:189213 )

• thick at P10 with lower nuclear density indicating changes in the extracellular matrix rather than increase in cell density

• increased outflow tract valve leaflet width in adults

increased heart right ventricle size ( J:189213 )

• increased area

heart right ventricle hypertrophy ( J:189213 )

thick ventricular wall ( J:189213 )

• in right ventricle

dilated heart ( J:189213 )

• near the apex

pulmonary valve regurgitation ( J:189213 )

• severe

increased systemic arterial systolic blood pressure ( J:189213 )

• with severe regurgitation at the pulmonic valve

liver/biliary system

liver/biliary system phenotype ( J:166890 )

N	• mice exhibit normal bile duct formation (J:166890)

Mouse Models of Human Disease		OMIM ID	Ref(s)
Alagille Syndrome 1; ALGS1		118450	J:189213

mortality/aging

partial neonatal lethality ( J:166890 )

• most mice die within 2 days of birth with few surviving beyond 4 weeks

partial postnatal lethality ( J:166890 )

• most mice die within 2 days of birth with few surviving beyond 4 weeks

liver/biliary system

liver hemorrhage ( J:166890 )

• multifoci

abnormal bile duct morphology ( J:166890 )

• absent or incompletely formed bile ducts near the portal veins

abnormal bile duct development ( J:166890 )

• biliary epithelial cells are unable to organize into tubules; portal vein mesenchyme is reduced

• epithelial cells fail to aggregate

hepatic necrosis ( J:166890 )

abnormal bile secretion ( J:166890 )

• accumulation of bile in liver parenchyma

cholestasis ( J:166890 )

jaundice ( J:166890 )

• at birth

homeostasis/metabolism

increased circulating bilirubin level ( J:166890 )

• total and conjugated

increased circulating cholesterol level ( J:166890 )

abnormal enzyme/ coenzyme level ( J:166890 )

• increased circulating gamma-glutamyl transferase

increased circulating alanine transaminase level ( J:166890 )

increased circulating alkaline phosphatase level ( J:166890 )

increased circulating aspartate transaminase level ( J:166890 )

increased lactate dehydrogenase level ( J:166890 )

• circulating

growth/size

decreased body weight ( J:166890 )

• at P25

postnatal growth retardation ( J:166890 )

• at birth and in mice that survive beyond 4 weeks, worsening over time

behavior/neurological

lethargy ( J:166890 )

• in mice that survive beyond 4 weeks, worsening over time

cardiovascular system

liver hemorrhage ( J:166890 )

• multifoci

integument

alopecia ( J:166890 )

• in mice that survive beyond 4 weeks, worsening over time

endocrine/exocrine glands

abnormal bile duct morphology ( J:166890 )

• absent or incompletely formed bile ducts near the portal veins

abnormal bile duct development ( J:166890 )

• biliary epithelial cells are unable to organize into tubules; portal vein mesenchyme is reduced

• epithelial cells fail to aggregate

Mouse Models of Human Disease		OMIM ID	Ref(s)
Alagille Syndrome 1; ALGS1		118450	J:166890

cn3

Jag1^tm1Frad/Jag1^tm1Frad
Tg(Cdh5-cre)7Mlia/0
Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor⁺
involves: 129 * 129S4/SvJaeSor * FVB/N

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

cardiovascular system

abnormal cardiac epithelial to mesenchymal transition ( J:189213 )

• temporarily delayed at E10.5

abnormal atrioventricular cushion morphology ( J:189213 )

• at E10.5, atrioventricular cushions exhibit rounded endocardial-derived cells that accumulate at the cushion interface and less dense, hypoplastic areas unlike in control mice

cn4

Jag1^tm1Frad/Jag1^tm1Frad
Tg(Mx1-cre)1Cgn/0
involves: 129 * C57BL/6 * CBA

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

hematopoietic system

hematopoietic system phenotype ( J:98129 )

N	• homozygous mutant mice exhibit normal hematopoiesis, including normal hematopoietic stem cell self-renewal and differentiation (J:98129)

cn5

Jag1^tm1Frad/Jag1^tm1Frad
Notch1^tm1Agt/Notch1^tm1Agt
Tg(Mx1-cre)1Cgn/0
involves: 129 * C57BL/6 * CBA

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

hematopoietic system

hematopoietic system phenotype ( J:98129 )

N	• homozygous mutant mice exhibit normal hematopoiesis, including normal hematopoietic stem cell self-renewal and differentiation (J:98129)