Phenotypes Associated with This Genotype

Genotype
MGI:6437232

• Allelic Composition: Adamts19^{tm4b(EUCOMM)Wtsi}/Adamts19^{tm4b(EUCOMM)Wtsi}
• Genetic Background: B6N(Cg)-Adamts19^{tm4b(EUCOMM)Wtsi}
• Cell Lines: MEPD1003_3_C02

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

cardiovascular system

abnormal aortic valve morphology ( J:287334 )

• at 3 weeks of age, 36% of mice show increased KLF2 expression in the endothelial cells, suggesting increased shear stress in the endothelial layer of aortic valves

• at 6 months of age, cellular features of diseased valves are consistent with a change toward a secretory valvular interstitial cell (VIC) phenotype

• however, no calcification is observed up to 9 months of age

abnormal aortic valve annulus morphology ( J:287334 )

• partial fusion at the annulus of the aortic valve leaflets shows increased collagen deposition at the hinges covering the raphe

abnormal aortic valve commissure morphology ( J:287334 )

• dysfunctional aortic valves exhibit thickened commissures

abnormal aortic valve cusp morphology ( J:287334 )

• dysfunctional aortic valves have a reduced opening, occasionally in a 'fish mouth' pattern with only two visible leaflets, resembling a functional fused bicuspid aortic valve (BAV)-like phenotype

• aortic valves appear denser with localized accumulation of melanocyte clusters in the leaflets; the extracellular matrix (ECM) appears disorganized throughout the leaflets

• in the hinge regions, valves show smaller collagen type I fibers, cells reminiscent of osteoblasts and increased cellular debris

aortic valve stenosis ( J:287334 )

• at 3 months of age, 38% of mice show aortic valve regurgitation and/or severe aortic stenosis

thick aortic valve ( J:287334 )

• at 6 months of age, aortic valves tend to be thicker with cellular debris, small bundles of collagen fibers and abundant proteoglycans, esp. at the leaflet tip

• aortic valves are significantly thickened by 9 months

thick aortic valve cusps ( J:287334 )

• aortic valves are thickened at the hinge regions of the leaflets

abnormal aortic valve flow ( J:287334 )

• mice exhibit progressive aortic valve dysfunction characterized by regurgitation and/or aortic stenosis

• at 3 months of age, ~20% of mice show abnormal blood flow in systole and increased systolic aortic pressure

• aortic peak pressures are significantly increased at 6 and 9 months of age

aortic valve regurgitation ( J:287334 )

• at 3 months of age, 27% of mice show aortic regurgitation in diastole; 38% of mice show aortic valve regurgitation and/or severe aortic stenosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
aortic valve disease		DOID:62		J:287334