title: Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy.
abstract: In skeletal muscle, dystroglycan (DG) is the central component of the dystrophin-glycoprotein complex (DGC), a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1) have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review focuses specifically on the animal (murine and others) model systems that have been developed with the aim of directly engineering DAG1 in order to study the DG function in skeletal muscle as well as in other tissues. In the last years, conditional animal models overcoming the embryonic lethality of the DG knock-out in mouse have been generated and helped clarifying the crucial role of DG in skeletal muscle, while an increasing number of studies on knock-in mice are aimed at understanding the contribution of single amino acids to the stability of DG and to the possible development of muscular dystrophy.
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, CNR c/o Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sciandra
authors.affiliation: School of Biochemistry, Bristol University, Bristol B58 1TD, UK.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Bigotti
authors.affiliation: Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Giardina
authors.affiliation: Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bozzi
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, CNR c/o Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, 00168 Roma, Italy ; School of Biochemistry, Bristol University, Bristol B58 1TD, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancaccio
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D049030:Dystroglycans / Q000235:genetics* / Q000378:metabolism; D016189:Dystrophin / Q000235:genetics; D005818:Genetic Engineering; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics* / Q000473:pathology
chemical_list: C483081:DAG1 protein, human; D016189:Dystrophin; D049030:Dystroglycans