Phenotypes Associated with This Genotype

Genotype
MGI:5771892

• Allelic Composition: Notch1^tm1Grid/Notch1⁺; Notch3^tm1Grid/Notch3^tm1Grid
• Genetic Background: involves: 129S1/Sv * C57BL/6

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

vision/eye

abnormal retina vasculature morphology ( J:227333 )

• increase in the number of endothelial tip cells at the angiogenic front of P5 retinas

• P8 retinas display areas of sheet-like endothelium that lacks defined arterioles and venules

• retinas show extensive presence of arteriovenous shunts and vascular tangles

abnormal retina blood vessel morphology ( J:227333 )

• increase in vessel density in retinas compared to either single mutant

• reduction in vessel outgrowth at P5 in retinas

• retinal capillaries exhibit gaps in pericyte coverage

• P5 retinas show altered vessel structures with pericytes located at a greater distance from the vessel lumen, indicative of pericyte dissociation

• the intracellular region between pericytes and endothelial cells appears wider, less dense and has visible large open spaces indicating that pericytes fail to associate properly with the endothelium

• retinal vessels of P5 mice show loss of mural cells

• P5 retinal capillaries exhibit numerous granular osmiophilic material in the vicinity of pericytes and not associated with endothelial cells

cardiovascular system

abnormal retina vasculature morphology ( J:227333 )

• increase in the number of endothelial tip cells at the angiogenic front of P5 retinas

• P8 retinas display areas of sheet-like endothelium that lacks defined arterioles and venules

• retinas show extensive presence of arteriovenous shunts and vascular tangles

abnormal retina blood vessel morphology ( J:227333 )

• increase in vessel density in retinas compared to either single mutant

• reduction in vessel outgrowth at P5 in retinas

• retinal capillaries exhibit gaps in pericyte coverage

• P5 retinas show altered vessel structures with pericytes located at a greater distance from the vessel lumen, indicative of pericyte dissociation

• the intracellular region between pericytes and endothelial cells appears wider, less dense and has visible large open spaces indicating that pericytes fail to associate properly with the endothelium

• retinal vessels of P5 mice show loss of mural cells

• P5 retinal capillaries exhibit numerous granular osmiophilic material in the vicinity of pericytes and not associated with endothelial cells

abnormal pericyte morphology ( J:227333 )

• a subset of pericytes in capillaries show altered cell morphology with overlapping cell processes that fail to tightly and continuously line the endothelium

• reduction in pericyte coverage and abnormal pericyte morphology along enlarged retinal venules at P5

abnormal vascular plexus formation ( J:227333 )

• at P8, mice maintain a hyper-vascularized retinal primary plexus

abnormal vascular smooth muscle morphology ( J:227333 )

• mice exhibit impaired arteriolar vascular smooth muscle cell differentiation at P5

abnormal venule morphology ( J:227333 )

• enlargement of venules in P5 retinas

arteriovenous malformation ( J:227333 )

• mice display severe retinal arteriovenous malformations

cellular

impaired basement membrane formation ( J:227333 )

• collagen IV deposition in retinal capillaries is severely disorganized and often in the open spaces of the capillary plexus and laminin deposition is abnormal indicating abnormal vascular basement membrane formation

muscle

abnormal vascular smooth muscle morphology ( J:227333 )

• mice exhibit impaired arteriolar vascular smooth muscle cell differentiation at P5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CADASIL 1		DOID:0111035	OMIM:125310	J:227333