Table 1.
Mouse models of human connective tissue disorders with valvular defects.
| Human Disease | Associated ECM Gene | Mouse Model | Human Valvular Defects Recapitulated in the Mouse Model | References |
|---|---|---|---|---|
| Williams-Beuren Syndrome | Elastin | Deletion (from Gtf2i to Fkbp6) (includes ELN) (most common deletion found in humans with WBS) | Supravalvular aortic stenosis (SVAS) | [125] |
| Loeys-Dietz Syndrome |
TGF-
βR1
TGF- βr2R2 TGF- β1 SMAD3 |
Loss-of-function mutations: -Tgfβr1M318R/+−Tgfβr2G357W/+ -Transgenic Tgfβr2 |
Aortic aneurysm Mitral valve prolapse |
[143] [144] [145] [146] |
| Cutis Laxa |
FBNL4
FBNL5 |
Fibulin-4R/R (reduced expression allele) |
Thickened aortic valve leaflets with stenosis and insufficiency | [145] [146] |
| Marfan Syndrome | FBN1 | Fbn1C1039G/+ | Mitral valve prolapse | [127] |
| Ehlers-Danlos Syndrome | COLVA1 | ColVa1+/− | No gross of functional valve defects | [20] |
| Stickler Syndrome | COLXIA1 | ColXIa1−/− | Thickened valve leaflets | [20] |
| Osteogenesis Imperfecta | COL1A2 | Col1a2−/− (oim/oim) | Myxomatous aortic valve leaflets | [117] |
| Fibrotic aortic valve disease-autosomal-dominant connective tissue disease | EMILIN-1 | Emilin1−/− | Marked progression of valve pathology that shows severe fibrosis, neovascularization and inflammation | [147] [148] |