Temporal in situ physiology and proteomics characterization of skeletal muscles from mdx5cv mice overexpressing JAG1


Topic:

Pre-Clinical Research

Poster Number: LB443

Author(s):

Felipe de Souza Leite, PhD, Boston Children's Hospital & Harvard Medical School, Jeffrey J. Widric, PhD, Boston Children's Hospital, Matthias R. Lambert, PhD, Vertex, João A. Paulo, PhD, Harvard Medical School, Tracy Zhang, PhD, Sanofi, James R. Conner, MSc, Boston Children's Hospital, Sheldon Oliveira, Boston Children's Hospital, Emanuela Gussoni, PhD, Boston Children's Hospital and Harvard Medical School, Steven Gygi, PhD, Harvard Medical School, Louis M . Kunkel, PhD, Boston Children's Hospital and Harvard Medical School

Introduction: The beneficial effects of the overexpression of Jagged-1 were described in escaper golden retriever muscular dystrophy (GRMD) dogs that had a near-normal life. Additionally, overexpression of Jag1 improved the phenotype in dystrophin-deficient zebrafish. Here, we show updated findings on a dystrophin-deficient mouse model overexpressing human JAG1 (mdx5cv-JAG1) compared with controls mdx5cv. Methods: Animals were studied at three time points: one, four, and twelve months. TA muscles were used for in situ physiology. Quadriceps muscles were used for proteomics. Results: (1) Muscle-specific overexpression of JAG1 leads to increased muscle mass starting from four months, resulting in higher ratios of muscle weight/body weight. (2) In situ physiology showed increased force in mdx5cv-JAG1 muscles from four- and twelve-month-old animals. (3) Proteomics data using muscles collected at the three time points show changes in metabolic and muscle-related pathways, and its interaction with essential proteins related to muscle repair and growth. Conclusion: Our data supports the beneficial role of JAG1 overexpression in dystrophin-deficient muscles and suggests an interaction of jagged-1 with muscle repair mechanisms.