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Morphoquantitative and ultrastructural aspects of the effects of Duchenne Muscular Dystrophy and congenital muscular dystrophy in basioccipital synchondrosis of Dmdmdx and largemyd mice

Grant number: 14/19605-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2015
Effective date (End): August 31, 2016
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Edson Aparecido Liberti
Grantee:Letícia Martins Santos
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Muscular Dystrophies (DM) are defined as a set of pathologies of genetic origin that affect the skeletal musculature. Duchenne Muscular Dystrophy (DMD) is the most severe and frequent type of muscular dystrophy, affecting 1 in every 3500 births of males. It is a genetic mutation, and the affected gene encodes the dystrophin protein, and its absence leads to rupture and necrosis of muscle fibers due to changes caused between the cytoskeleton and the extracellular matrix of the plasma membrane. Congenital Muscular Dystrophy (DMC) is also considered one of the main types of muscular dystrophy. It is a heterogeneous group of autosomal diseases that has the muscular impairment noticed from birth or in the first months of life. New forms of DMC have recently been linked to mutations in genes encoding glycosyltransferase enzymes, which contribute to the glycosylation of the ±-DG protein, an essential member in the formation and function of the muscular DGC complex. The base of the skull is a fundamental region in craniofacial development, and the synchondroses present in it, consisting of primary cartilage, are important centers of craniofacial growth, since they ossify by the process of endochondral ossification. Although dystrophin deficiency and ±-DG protein glycosylation do not directly affect the development of cartilage tissue, it has been reported that muscle action interferes with this process, which gives DM a potential for craniofacial growth change. Thus, in the present study, the use of histology, morphometry and ultrastructural techniques will evaluate the effects of DMD and DMC on the basioccipital synchondrosis (sbo), an important center of craniofacial growth in mice. The experimental models are the Dmdmdx mice, being the animal model most used for the study of DMD, despite its mild phenotype, and the Largemyd mutant mice that represent DMC with severe myopathic phenotype similar to that seen in humans.