Extraocular muscle is spared upon complete laminin α2 chain deficiency: Comparative expression of laminin and integrin isoforms

Different Impact of ALS on Laminin Isoforms in Human Extraocular Muscles versus Limb Muscles

“…21,[43][44][45] In addition to laminin 211, normal EOMs also have laminins 411, 511, 421, and 521 in the BM of their muscle fibers, a feature that we have previously proposed to be instrumental in the selective sparing of the EOMs in merosin-deficient congenital muscle dystrophy. 27,46 Here we showed that in normal aging there was a decrease or absence of Ln␣4 in the EOMs, without any signs of BM disruption. Therefore, we proposed that Ln␣4 is not indispensable for the maintenance of muscle fiber integrity in the human EOMs.…”

Skeletal muscle laminin and MDC1A: pathogenesis and treatment strategies

“…In extraocular muscles, which have a number of differences from other skeletal muscles, the laminin α4 chain is strongly expressed in the basement membrane adjoining the sarcolemma, and its expression is further enhanced in the extraocular muscle of dy 3K / dy 3K animals. Interestingly, laminin α2 chain-deficient extraocular muscles are spared from dystrophic changes, and it has been hypothesized that binding of the laminin α4 chain to integrin α7β1 may protect the extraocular muscles from damage [100,101]. …”

Intrinsic laryngeal muscles are spared from degeneration in the dy3k/dy3k mouse model of congenital muscular dystrophy type 1A

“…Interestingly, some muscles remain unaffected during the course of these diseases. The extraocular muscle (EOM) is spared upon dystrophin deficiency, both in patients with Duchenne muscular dystrophy and in the mdx mouse1 and in mouse models for sarcoglycan13 and laminin α2 chain deficiency 10, 12. Moreover, intrinsic laryngeal muscles (ILM) were recently demonstrated to be spared in the dystrophin‐deficient mdx mouse 6, 15.…”

“…Understanding why certain muscle groups are protected from degeneration should contribute to the knowledge of the underlying pathogenetic mechanisms of DGC‐associated muscular dystrophies. For example, it is hypothesized that sparing of laminin α2 chain‐deficient EOM is due to an increased expression of laminin α4 chain in the EOM basement membrane 10. Normally, laminin α4 chain is restricted to capillaries within skeletal muscle.…”

“…However, upon laminin α2 chain deficiency, expression is increased at the muscle basement membrane 11, 14. Notably, EOM basement membranes are particularly rich in laminin α4 chain 10. Furthermore, integrin α7Bβ1D is one of the main laminin α2 chain receptors in mature muscle 7.…”