| First Author | Mi-Mi L | Year | 2020 |
| Journal | PLoS One | Volume | 15 |
| Issue | 1 | Pages | e0226138 |
| PubMed ID | 31899774 | Mgi Jnum | J:283380 |
| Mgi Id | MGI:6384784 | Doi | 10.1371/journal.pone.0226138 |
| Citation | Mi-Mi L, et al. (2020) In vivo elongation of thin filaments results in heart failure. PLoS One 15(1):e0226138 |
| abstractText | A novel cardiac-specific transgenic mouse model was generated to identify the physiological consequences of elongated thin filaments during post-natal development in the heart. Remarkably, increasing the expression levels in vivo of just one sarcomeric protein, Lmod2, results in ~10% longer thin filaments (up to 26% longer in some individual sarcomeres) that produce up to 50% less contractile force. Increasing the levels of Lmod2 in vivo (Lmod2-TG) also allows us to probe the contribution of Lmod2 in the progression of cardiac myopathy because Lmod2-TG mice present with a unique cardiomyopathy involving enlarged atrial and ventricular lumens, increased heart mass, disorganized myofibrils and eventually, heart failure. Turning off of Lmod2 transgene expression at postnatal day 3 successfully prevents thin filament elongation, as well as gross morphological and functional disease progression. We show here that Lmod2 has an essential role in regulating cardiac contractile force and function. |
