RT Journal Article
T1 Deletion of the Wilms' Tumor Suppressor Gene in the Cardiac Troponin-T Lineage Reveals Novel Functions of WT1 in Heart Development.
A1 Díaz Del Moral, Sandra
A1 Barrena, Silvia
A1 Hernández-Torres, Francisco
A1 Aránega, Amelia
A1 Villaescusa, José Manuel
A1 Gómez Doblas, Juan José
A1 Franco, Diego
A1 Jiménez-Navarro, Manuel
A1 Muñoz-Chápuli, Ramón
A1 Carmona, Rita
K1 Wilms’ tumor suppressor gene
K1 calcium homeostasis
K1 cardiac development
K1 cardiomyocytes
K1 potassium channels
AB Expression of Wilms' tumor suppressor transcription factor (WT1) in the embryonic epicardium is essential for cardiac development, but its myocardial expression is little known. We have found that WT1 is expressed at low levels in 20-25% of the embryonic cardiomyocytes. Conditional ablation of WT1 using a cardiac troponin T driver (Tnnt2 Cre ) caused abnormal sinus venosus and atrium development, lack of pectinate muscles, thin ventricular myocardium and, in some cases, interventricular septum and cardiac wall defects, ventricular diverticula and aneurisms. Coronary development was normal and there was not embryonic lethality, although survival of adult mutant mice was reduced probably due to perinatal mortality. Adult mutant mice showed electrocardiographic anomalies, including increased RR and QRS intervals, and decreased PR intervals. RNASeq analysis identified differential expression of 137 genes in the E13.5 mutant heart as compared to controls. GO functional enrichment analysis suggested that both calcium ion regulation and modulation of potassium channels are deeply altered in the mutant myocardium. In summary, together with its essential function in the embryonic epicardium, myocardial WT1 expression is also required for normal cardiac development.
SN 2296-634X
YR 2021
FD 2021-07-22
LK https://hdl.handle.net/10668/24621
UL https://hdl.handle.net/10668/24621
LA en
DS RISalud
RD Apr 14, 2025