Mechanotransduction, nuclear architecture and epigenetics in Emery Dreifuss Muscular Dystrophy: tous pour un, un pour tous

Figures & data

Table 1. Mouse models of Emery Dreifuss Muscular Dystrophy.

Lmna mouse	Phenotype	Comment
Lmna Δ8-11	Homozygous mice show an abnormal gait with a stiff walking posture by the 4^th week. Scoliosis/kyphosis are documented.	A truncated isoform of Lmna (Δ8-11) is present; strain cannot be considered “null”.
Lmna GT	Homozygous mice hunched posture and abnormal gait, characterized by splayed hind legs from day postnatal day 13.	No truncated isoform is present; can be thus considered Lmna null.
Lmna H222P	At adulthood, male homozygous mice display reduced locomotion activity with abnormal stiff walking posture.	Heterozygous Lmna H222P causes autosomal dominant EDMD in humans
Lmna ΔK32	Homozygous mice show a delay in striated muscle maturation, reduced fat tissue and hypoglycemia leading to premature death (by the 3rd week).	The loss of lysine 32 in the N-terminal domain of LMNA leads to a severe congenital muscular dystrophy (CMD).

Figure 1. Schematic representation of Lamin dependent mechanotransduction. Nuclear lamina works in couple with the mechanotransductor machinery to convert mechanical stimuli into epigenetic changes including: Histone modification, LAD higher order structures and PcG organization (a, b) In EDMD, the compromised mechano-properties of aberrant form of Lamin A/C could increase the sensitivity of the nuclei to mechanical stress resulting in: loss of LAD conformation, PcG bodies dispersion and aberrant gene expression.