Pathological alterations in the gastrointestinal tract of a porcine model of DMD

Abstract

Background Patients with Duchenne muscular dystrophy (DMD) develop severe skeletal and cardiac muscle pathologies, which result in premature death. Therefore, the current therapeutic efforts are mainly targeted to correct dystrophin expression in skeletal muscle and heart. However, it was reported that DMD patients may also exhibit gastrointestinal and nutritional problems. How the pathological alterations in gastrointestinal tissues contribute to the disease are not fully explored. Results Here we employed the CRISPR/Cas9 system combined with somatic nuclear transfer technology (SCNT) to establish a porcine model of DMD and explored their pathological alterations. We found that genetic disruption of dystrophin expression led to morphological gastrointestinal tract alterations, weakened the gastrointestinal tract digestion and absorption capacity, and eventually led to malnutrition and gastric dysfunction in the DMD pigs. Conclusions This work provides important insights into the pathogenesis of DMD and highlights the need to consider the gastrointestinal dysfunction as an additional therapeutic target for DMD patients.

A scalable, clinically severe pig model for Duchenne muscular dystrophy

“…S6C " type="url"/> ). Gastrointestinal alterations were also observed in cloned Bama minipigs with DMD exon 51 mutations ( Zou et al, 2021 ).…”

“…None of the pigs reached sexual maturity; thus, cloning or blastocyst complementation ( Matsunari et al, 2018 ) were the only ways to propagate the model. Similarly, Bama miniature pigs cloned from gene-edited cells with DMD exon 51 mutations had a maximum life expectancy of 12 weeks ( Zou et al, 2021 ).…”

CRISPR applications for Duchenne muscular dystrophy: From animal models to potential therapies

“…More recently, Bama miniature pigs with InDels in DMD exon 51 were generated by CRISPR editing of fetal fibroblasts and SCNT. Nine of 15 live piglets carried DMD mutations but died within 12 weeks of age (Zou et al, 2021 ).…”

Advances in CRISPR-Based Functional Genomics and Nucleic Acid Detection in Pigs

“…Pigs ( Sus scrofa ) are closely related to humans in terms of anatomy, genetics and physiology. The generation of DMD knockout pig models using CRISPR/Cas9 technology may potentially pave the way for new treatments for patients ( Yu et al, 2016 ; Zou et al, 2021 ).…”