| First Author | Park K-S | Year | 2021 |
| Journal | bioRxiv | Mgi Jnum | J:307416 |
| Mgi Id | MGI:6720922 | Doi | 10.1101/2021.02.23.432554v1 |
| Citation | Park K-S, et al. (2021) Cardiac pathologies in mouse loss of imprinting models are due to misexpression of H19 long noncoding RNA. bioRxiv |
| abstractText | Maternal loss of imprinting (LOI) at the H19/IGF2 locus results in biallelic IGF2 and reduced H19 expression and is associated with Beckwith Wiedemann syndrome (BWS). We use mouse models for LOI to understand the relative importance of Igf2and H19 mis-expression in BWS phenotypes. Here we focus on cardiovascular phenotypes and show that neonatal cardiomegaly is exclusively dependent on increased Igf2. Circulating IGF2 binds cardiomyocyte receptors to hyperactivate mTOR signaling, resulting in cellular hyperplasia and hypertrophy.These Igf2-dependent phenotypes are transient: cardiac size returns tonormal once Igf2expression is 33suppressed postnatally.However, reduced H19expression is sufficient to cause progressiveheart34pathologies including fibrosisand reduced ventricular function.In the heart, H19 expression is concentrated predominantly in endothelial cells (ECs) and regulates EC differentiation both, in vivoand in vitro. Finally, we establish novel mouse models to show that cardiac phenotypes depend on H19 lncRNA interactions with let7microRNA |
