Modeling amyotrophic lateral sclerosis in hSOD1 transgenic swine

Area of Science:

• Neuroscience
• Genetics
• Animal Models

Background:

• Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease with sporadic and familial forms.
• Familial ALS (FALS) is often linked to mutations in the Cu/Zn superoxide dismutase (SOD1) gene.
• Current mouse models (G93A) expressing mutated human SOD1 (hSOD1) show limitations in fully replicating human ALS pathology.

Purpose of the Study:

• To develop the first swine model for Amyotrophic Lateral Sclerosis (ALS) to improve disease modeling.
• To create a more accurate preclinical model for ALS by leveraging swine's physiological similarities to humans.

Main Methods:

• Developed a SOD1(G93A) vector for high and stable transgene expression in primary porcine adult male fibroblasts (PAF).
• Utilized somatic cell nuclear transfer (SCNT) with transfected PAF cells to create SOD1(G93A) embryos.
• Transferred embryos to recipient sows, resulting in the birth and survival of SOD1(G93A) piglets.

Main Results:

• Successfully produced the first generation of SOD1(G93A) transgenic piglets.
• Confirmed transgene integration and expression of human SOD1(G93A) in swine tissues.
• Piglets survived, reached adulthood, and are undergoing comprehensive phenotypical characterization.

Conclusions:

• The developed SOD1(G93A) swine model represents a significant advancement in ALS research.
• This model may serve as a crucial bridge between rodent studies and human ALS clinical applications.
• Swine offer a promising alternative to rodent models for studying complex human diseases like ALS.