PLEC, encoding plectin, is a gene crucial for cytoskeletal function as plectin serves as a linker of intermediate filaments, expressed in numerous cell types. Plectin consists of three main domains determining its functionality, and it is involved in pathways related to cell structure and organization, which is of overall biological importance for maintaining cell integrity. Genetically manipulated mouse and cell models, including those that are plectin-deficient or lack a specific skeletal-muscle-expressed plectin isoform, are powerful tools for functional studies of PLEC [1,2].

Molecular defects of PLEC lead to a group of rare heritable disorders called plectinopathies. These include autosomal dominant epidermolysis bullosa simplex (EBS-Ogna), limb-girdle muscular dystrophy (LGMD), aplasia cutis congenita (ACC), and autosomal recessive forms such as EBS with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and/or congenital myasthenic syndrome (EBS-MyS). In EBS-MD patients and plectin-deficient mice, skeletal muscle biopsies show severe dystrophic features like fiber size variation, myofibrillar changes, mitochondrial alterations, and protein aggregates. Ultrastructurally, there are myofibril and sarcomere disorganization. These mouse models reveal PLEC's role in maintaining normal muscle structure and function [1,2].

In conclusion, PLEC is essential for cytoskeletal organization and maintaining cell integrity, especially in muscle cells. The study of PLEC-deficient mouse models has significantly contributed to understanding its role in plectinopathies, highlighting its importance in muscle-related disease areas.

References:

1. Vahidnezhad, Hassan, Youssefian, Leila, Harvey, Nailah, Zeinali, Sirous, Uitto, Jouni. 2022. Mutation update: The spectra of PLEC sequence variants and related plectinopathies. In Human mutation, 43, 1706-1731. doi:10.1002/humu.24434. https://pubmed.ncbi.nlm.nih.gov/35815343/

2. Zrelski, Michaela M, Kustermann, Monika, Winter, Lilli. 2021. Muscle-Related Plectinopathies. In Cells, 10, . doi:10.3390/cells10092480. https://pubmed.ncbi.nlm.nih.gov/34572129/