In humans, multiple genes have been implicated in muscular dystrophy (MD); in addition, in many cases, a specific gene is implicated in multiple forms of the disease. This report describes fly models of muscular dystrophy related to the human gene lamin A/C gene (LMNA), which encodes an intermediate filament protein that is a component of the nuclear lamina. There are multiple lamins in both humans and flies: the human genes LMNA, LMNB2 and LMNB1 are orthologous to fly genes Dmel\Lam and Dmel\LamC. Classical amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for both fly genes.
The human LMNA gene is implicated in multiple other diseases (see MIM:150330), including Hutchinson-Gilford progeria syndrome (MIM:176670, FBhh0000176) and dilated cardiomyopathy 1A (MIM:115200, FBhh0000157). Forms of muscular dystrophy associated with LMNA include Emery-Dreifuss muscular dystrophy 2 and 3 (MIM:181350, MIM:616516, FBhh0000209), and LMNA-related congenital muscular dystrophy (MIM:613205, FBhh0000293). See also the human disease reports 'laminopathies' (FBhh0000264) and 'dilated cardiomyopathy 1A' (FBhh0000157).
Multiple UAS and heat-shock constructs of the human Hsap\LMNA gene have been introduced into flies, including wild-type LMNA, mutant protein isoforms, and deletion constructs.
Many modifications of the fly LamC gene that correspond to variants implicated in MD have been characterized; see the Disease-Implicated Variants' table below.
Amorphic alleles of both Dmel\LamC and Dmel\Lam are lethal, usually in the larval or pupal stage. For hypomorphic alleles, surviving adults show reduced viability, locomotion defects, and various visible phenotypes. Genetic and physical interactions have been described for both genes; see below and in the LamC and Lam gene reports.
[updated Oct. 2022 by FlyBase; FBrf0222196]
A form of congenital muscular dystrophy (MIM:613205) is caused by heterozygous mutation in the LMNA gene. Several types described as Emery-Dreifuss muscular dystrophies are also associated with the LMNA gene (MIM:181350, MIM:616516). [from MIM:150330; 2020.04.29]
The Lamin A/C gene (LMNA) encodes a component of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. [from Gene Cards, LMNA; 2016.03.29]
Moderate-scoring ortholog of human genes LMNA, LMNB2 and LMNB1 (2 Drosophila to 3 human). Dmel\LamC shares 35-38% identity and 54-58% similarity with the human genes.
