Role of Laminin-211 in cardiac and smooth muscle

Muscular dystrophies, including congenital muscular dystrophy type 1A (LAMA2-CMD), are associated with enormous personal, social and economic burdens. LAMA2-CMD patients display muscle wasting, they are not able to walk and die in early teens due to multiple tissue defects. Our understanding of pathogenic mechanisms underlying LAMA2-CMD in muscle and non-muscle tissue is still limited and consequently there is no treatment for this devastating disease, a treatment that is desperately needed.
LAMA2-CMD is caused by mutations in the gene encoding laminin α2 chain that together with β1 and γ1 chains forms the heterotrimeric protein laminin-211. This extracellular matrix protein is highly expressed in the neuromuscular system, but it is also produced in cardiovascular, respiratory and digestive systems. Cardiomyopathy, respiratory failure and feeding difficulties are the common features of LAMA2-CMD that significantly compromise patients’ activity, everyday life quality and longevity. Yet, relatively little is known about those non-skeletal muscle complications associated with the disease. We would like to shed more light on laminin-211 function in heart and smooth muscles (lung, intestine, stomach and blood vessels) and non-skeletal manifestations in LAMA2-CMD by generating conditional knock-out mice lacking laminin-211 in those tissues. This approach will hopefully help to get a complete picture of LAMA2-CMD pathology and help to understand the role of laminins in multiple tissues.