Plec-flox Mouse

Plec, encoding plectin, is a gene crucial for cytoskeletal linking of intermediate filaments [1,2,3]. Plectin, a giant cytoskeletal cross-linker and intermediate filament stabilizing protein, consists of three main domains determining its functionality [2]. It is expressed in many cell types and is involved in maintaining the structural integrity of cells [1,2,3]. Genetically manipulated mouse and cell models, such as plectin-deficient mice, are powerful tools to study the functional and molecular consequences of Plec defects [3].

Mutations in the Plec gene lead to a group of rare heritable disorders called plectinopathies [2]. These include autosomal dominant epidermolysis bullosa simplex (EBS-Ogna), limb-girdle muscular dystrophy (LGMD), aplasia cutis congenita (ACC), and autosomal recessive forms like EBS with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and/or congenital myasthenic syndrome (EBS-MyS) [2]. Skeletal muscle biopsies from EBS-MD patients and plectin-deficient mice showed severe dystrophic features, including variation in fiber size, degenerative myofibrillar changes, mitochondrial alterations, and pathological desmin-positive protein aggregates [3]. Ultrastructurally, Plec mutations cause disorganization of myofibrils and sarcomeres, Z-and I-band alterations, autophagic vacuoles, cytoplasmic bodies, and misplaced and degenerating mitochondria [3]. In addition, novel Plec variants have been associated with infantile cholestasis [1]. Immunofluorescence staining of liver samples from affected infants revealed abnormal plectin signals and reduced colocalization with cytokeratin 8 [1].

In conclusion, Plec is essential for maintaining cytoskeletal integrity in various cell types. Studies using gene-knockout or conditional-knockout mouse models have significantly contributed to understanding its role in plectinopathies, including skin, muscle, and liver-related disorders such as epidermolysis bullosa, muscular dystrophy, and infantile cholestasis. These findings provide insights into the underlying mechanisms of these diseases and may help develop targeted therapies.