Emerin-Lacking Mice Show Minimal Motor and Cardiac Dysfunctions with Nuclear-Associated Vacuoles

Abstract

Emery-Dreifuss muscular dystrophy is an inherited muscular disorder clinically characterized by slowly progressive weakness affecting humero-peroneal muscles, early joint contractures, and cardiomyopathy with conduction block. The X-linked recessive form is caused by mutation in the EMD gene encoding an integral protein of the inner nuclear membrane, emerin. In this study, mutant mice lacking emerin were produced by insertion of a neomycin resistance gene into exon 6 of the coding gene. Tissues taken from mutant mice lacked emerin. The mutant mice displayed a normal growth rate indistinguishable from their littermates and were fertile. No marked muscle weakness or joint abnormalities were observed; however, rotarod test revealed altered motor coordination. Electrocardiography showed mild prolongation of atrioventricular conduction time in emerin-lacking male mice older than 40 weeks of age. Electron microscopic analysis of skeletal and cardiac muscles from emerin-lacking mice revealed small vacuoles, which mostly bordered the myonuclei. Our results suggest that emerin deficiency causes minimal motor and cardiac dysfunctions in mice with a structural fragility of myonuclei.

Mouse models of the laminopathies

“…Cultured primary myoblasts from Emd null mice also showed a delay in fusing to form myotubes, which correlated with prolonged Rb1 hyperphosphorylation [21]. Despite these anomalies, mice (at least 1 year old) lacking emerin do not develop muscular dystrophy or cardiac conduction defects, suggesting that, in mice, loss of emerin may have few pathological consequences [21,23].…”

The lim domain only protein 7 is important in zebrafish heart development

“…In this instance, emerin would exert effects downstream of LMO7 in the development of the conduction system. The role of emerin in the development of the conduction system is far from understood, and emerin-lacking mice for example show minimal motor and cardiac dysfunctions (Ozawa et al, 2006). However, electrocardiography showed mild prolongation of atrioventricular conduction time in emerin-lacking male mice older than 40 weeks of age (Ozawa et al, 2006).…”

Nuclear lamins: key regulators of nuclear structure and activities

“…Loss of the emr-1 gene resulted in apparently normal mice with minimal motor and cardiac dysfunctions that probably result from retarded muscle regeneration [152,153]. Mutations in the mouse LBR gene result in ichthyosis [154].…”