| First Author | Gawlik KI | Year | 2025 |
| Journal | Matrix Biol | Volume | 141 |
| Pages | 47-66 | PubMed ID | 40854378 |
| Mgi Jnum | J:372530 | Mgi Id | MGI:8247484 |
| Doi | 10.1016/j.matbio.2025.08.006 | Citation | Gawlik KI, et al. (2025) Laminin gamma1 chain is essential for the cardiorespiratory and muscular systems. Matrix Biol |
| abstractText | Laminins are basement membrane components that regulate a plethora of biological processes. Despite decades of research, the exact roles of laminins in different tissues and in organogenesis remain to be elucidated. Here, we investigated the function of laminin gamma1 chain in heart, lung and other tissues by generating a mouse that lacks laminin gamma1 in cells expressing SM22alpha (Tagln) (LMgamma1 flox/SM22alpha Cre mouse, referred to as LMgamma1KO). Laminin gamma1 deletion led to basement membrane disruption around cardiomyocytes, smooth muscle cells, alveolar cells and skeletal muscle. This, in turn, led to perinatal death of conditional LMgamma1KO mice. Synchrotron-based imaging revealed developmental heart abnormalities: ventricular and atrioventricular septal defects. Lung tissue from embryos and newborns showed impaired alveolization and this defect was not reversed ex vivo. We also created adult inducible laminin gamma1 knockout mice (iLMgamma1KO) with targeted knockdown in all tissues, and they exhibited decreased contractility of smooth muscle in colonic and arterial tissue. Finally, both LMgamma1KO neonates and iLMgamma1KO adults displayed severe dystrophic features in skeletal muscle. In summary, our study reveals novel roles for laminin gamma1 chain and basement membranes in heart, lung, skeletal and smooth muscle. Compromising basement membranes around various cell types expressing SM22alpha during embryonic development did not impair early organogenesis of lung, heart and skeletal muscle, but rather disturbed late developmental events in these tissues. Our results could help to understand clinical implications for patients with laminin alpha2 chain mutations (muscular dystrophy) and laminin alpha4 mutations (cardiomyopathy), but also for patients with congenital heart disease and lung diseases. |
