Akash Agrawal
Pronouns: He/Him
Research Mentor(s): Mohammed Akaaboune
Research Mentor School/College/Department: Molecular, Cellular and Developmental Bi / LSA
Program:
Authors: Akash Agrawal, Mohammed Akaaboune
Session: Session 5: 2:40 pm – 3:30 pm
Poster: 70
Abstract
Duchenne’s muscular dystrophy (DMD) is characterized by cycles of rapid muscle degeneration and subsequent regeneration, leading to long-term muscle tissue degradation. DMD is caused by a mutation in the dystrophin gene. Dystrophin-deficient mdx mice, however, have nearly a normal life span despite the presence of muscular dystrophy, while mice deficient in dystrophin and the dystrophin-related protein utrophin exhibit severe muscular phenotypes that resemble typical signs of DMD in humans, indicating that utrophin attenuates the effects of dystrophin deficiency. In this work, we generate a triple knockout a-syntrophin (asyn), a-dystrobrevin (adbn), and dystrophin mouse that, despite upregulation of utrophin, shows severe progressive muscular dystrophy, progressive spinal Kyphosis deformity, persistent muscle necrosis over time, profound alterations in their neuromuscular junction, muscle paralysis, and death. All these abnormalities resemble the severe muscular dystrophy seen in Duchenne muscular dystrophy. These abnormalities are distinct from single (asyn, adbn, mdx) or double mutants (asyn-/-: adbn-/-), (asyn-/-: mdx), and (adbn-/-: mdx), which have a nearly normal lifespan. Thus, this mouse model should provide an alternative and improved model for underrating Duchenne muscular dystrophy.
