Morphological evaluation of cardiomyopathy in Golden Retriever dogs affected by muscular dystrophy

• Grant number: 13/25957-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2014
• End date: June 01, 2015
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Julieta Rodini Engracia de Moraes
• Grantee: Lygia Maria Mouri Malvestio
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil

Abstract

The Duchenne muscular dystrophy (DMD) and its milder variant, Becker muscular dystrophy (BMD), are the most common recessive diseases linked to the X chromosome characterized by a mutation in the gene encoding dystrophin. Dystrophin is responsible for connections between the intracellular medium, the actin cytoskeleton and/or the sarcomeric structure and external basement membrane. Changes in dystrophin expression induce clinical signs of muscle weakness with rapid progression Cardiac complications are common and are a major cause of morbidity and mortality in DMD and BMD. The dog Golden Retriever Muscular Dystrophy (GRMD) is the best experimental model for DMD, with genotypic and phenotypic manifestations closely of human disease. Similar to patients with DMD, heart failure is a major cause of death in GRMD animals. However, in GRMD animals the cardiac manifestations are delayed and milder when compared to those observed in skeletal muscle. This led us to speculate whether compensatory mechanisms would be involved in maintaining cardiac structure thus delaying the manifestation of clinical signs. Recent work from our collaboration group showed in cardiomyocytes from MDX mice (murine model of DMD) an increase of proteins expression from intercalated disk to compensate structural fragility due lack dystrophin. The main of this work is to elucidate the mechanisms responsible for delay of cardiac manifestations in GRMD animals by analyzing of proteins presents in the cytoskeleton, the contractile machinery and intercalated disc of cardiomyocytes from GRMD animals.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ISABELA M. MARTINS; LYGIA M.M. MALVESTIO; JAIR R. ENGRACIA-FILHO; GUSTAVO S. CLAUDIANO; FLÁVIO R. MORAES; JULIETA R.E. MORAES. O papel dos mastócitos na patogênese da distrofia muscular de Duchenne em cães Golden Retriever. Pesquisa Veterinária Brasileira, v. 40, n. 10, p. 791-797, 2020-12-14. (13/25957-6)

ENGRACIA DE MORAES, JULIETA RODINI; MOURI MALVESTIO, LYGIA MARIA; MARTINS, ISABELA MANCINI; ERDMANN MOSKO, PATRICIA REGINA; ENGRACIA FILHO, JAIR RODINI; DE MORAES, FLAVIO RUAS. Aspectos relevantes da distrofia muscular do Golden Retriever para o estudo da distrofia muscular de Duchenne em humanos. Ciência Rural, v. 47, n. 10, 2017. (13/25957-6)