| First Author | Gawlik KI | Year | 2018 |
| Journal | Matrix Biol | Volume | 70 |
| Pages | 36-49 | PubMed ID | 29544677 |
| Mgi Jnum | J:271080 | Mgi Id | MGI:6279578 |
| Doi | 10.1016/j.matbio.2018.02.024 | Citation | Gawlik KI, et al. (2018) Laminin alpha1 reduces muscular dystrophy in dy(2J) mice. Matrix Biol 70:36-49 |
| abstractText | Muscular dystrophies, including laminin alpha2 chain-deficient muscular dystrophy (LAMA2-CMD), are associated with immense personal, social and economic burdens. Thus, effective treatments are urgently needed. LAMA2-CMD is either a severe, early-onset condition with complete laminin alpha2 chain-deficiency or a milder, late-onset form with partial laminin alpha2 chain-deficiency. Mouse models dy(3K)/dy(3K) and dy(2J)/dy(2J), respectively, recapitulate these two forms of LAMA2-CMD very well. We have previously demonstrated that laminin alpha1 chain significantly reduces muscular dystrophy in laminin alpha2 chain-deficient dy(3K)/dy(3K) mice. Among all the different pre-clinical approaches that have been evaluated in mice, laminin alpha1 chain-mediated therapy has been shown to be one of the most effective lines of attack. However, it has remained unclear if laminin alpha1 chain-mediated treatment is also applicable for partial laminin alpha2 chain-deficiency. Hence, we have generated dy(2J)/dy(2J) mice (that express a substantial amount of an N-terminal truncated laminin alpha2 chain) overexpressing laminin alpha1 chain in the neuromuscular system. The laminin alpha1 chain transgene ameliorated the dystrophic phenotype, restored muscle strength and reduced peripheral neuropathy. Thus, these findings provide additional support for the development of laminin alpha1 chain-based therapy for LAMA2-CMD. |
