Lmo7 is dispensable for skeletal muscle and cardiac function

Abstract

Emery-Dreifuss muscular dystrophy (EDMD) is a degenerative disease primarily affecting skeletal muscles in early childhood as well as cardiac muscle at later stages. EDMD is caused by a number of mutations in genes encoding proteins associated with the nuclear envelope (e.g., Emerin, Lamin A/C, and Nesprin). Recently, a novel protein, Lim-domain only 7 ( lmo7) has been reported to play a role in the molecular pathogenesis of EDMD. Prior in vitro and in vivo studies suggested the intriguing possibility that Lmo7 plays a role in skeletal or cardiac muscle pathophysiology. To further understand the in vivo role of Lmo7 in striated muscles, we generated a novel Lmo7-null ( lmo7−/−) mouse line. Using this mouse line, we examined skeletal and cardiac muscle physiology, as well as the role of Lmo7 in a model of muscular dystrophy and regeneration using the dystrophin-deficient mdx mouse model. Our results demonstrated that lmo7−/− mice had no abnormalities in skeletal muscle morphology, physiological function, or regeneration. Cardiac function was also unaffected. Moreover, we found that ablation of lmo7 in mdx mice had no effect on the observed myopathy and muscular regeneration exhibited by mdx mice. Molecular analyses also showed no changes in dystrophin complex factors, MAPK pathway components, and Emerin levels in lmo7 knockout mice. Taken together, we conclude that Lmo7 is dispensable for skeletal muscle and cardiac physiology and pathophysiology.

LMO7 deficiency reveals the significance of the cuticular plate for hearing function

“…3d), consistent with the strategy to insert the gene trap cassette after exon 1. Our conclusion that the Lmo7 gene trap mouse does not represent a global Lmo7 KO mouse model is consistent with a previous study by Lao et al 32 . We therefore used CRISPR/Cas9 to generate a variety of mice with potentially deleterious mutations in the Lmo7 gene.…”

“…LMO7 contains a calponin homology (CH) domain, a PDZ domain, and a LIM domain, and was reported to be involved in protein-protein interactions at adherens junctions and focal adhesions 28,29 . LMO7 deficiencies have been reported to increase susceptibility to spontaneous lung cancer and contribute to the pathology of Emery-Dreifuss Muscular Dystrophy (EDMD) 30,31 , although the latter hypothesis is controversial 32 . In addition, LMO7 was revealed to play a role in the regulation of actin dynamics through the Rho-dependent MRTF-SRF signaling pathway 33 .…”

Diseases of the Nucleoskeleton

“…Surprisingly, loss of Lmo7 expression in mice using different gene-targeting approaches and a different genetic background failed to exhibit skeletal muscle or cardiac dysfunction nor have defective Rb and MAPK signaling (151). The authors of this study suggested the first Lmo7-null mouse line generated by Lmo7 gene-trap technology may have only removed the largest Lmo7 isoform, which is the major isoform in skeletal muscle (145,260), whereas their mice lacked expression of all Lmo7 isoforms.…”

Knockdown of Lmo7 inhibits chick myogenesis

“…Recently, contradictory results have been reported regarding the role of Lmo7 during mammalian skeletal muscle differentiation. Mull et al [18] described that Lmo7-null mice had decreased fiber size and impaired skeletal muscle function, whereas Lao et al [13] reported that Lmo7 À/À mice had no abnormalities in skeletal muscle morphology, physiological function, or regeneration. One possible explanation for these contradictory results could be related to differences in the generation of Lmo7 À/À mice.…”

“…Mull et al [18] reported that Lmo7-null mice had decreased fiber size and impaired skeletal muscle function, whereas Lao et al [13] described that Lmo7 À/À mice had no abnormalities in skeletal muscle morphology, physiological function, or regeneration. The chick myoblast primary culture is a robust in vitro model of myogenesis.…”