Effect of genetic background on onset and disease progression in the SOD1-G93A model of amyotrophic lateral sclerosis

Abstract

Knowledge of the potential effect of genetic background in disease models is important. The SOD1-G93A transgenic mouse is the most widely used model in amyotrophic lateral sclerosis (ALS). Since these animals show considerable variability both in the onset and the progression of the disease, this study aimed to characterize the potential differences between the two most widely used strains, C56BL/6 (B6) and B6SJL. A rotarod test was carried out to assess strength and motor coordination, while electrophysiology tests were performed to evaluate the function of upper and lower motor neurons. Survival of the animals and motor neuron loss were also studied. The results did not show any background effect regarding the rotarod test, despite the differences in the pattern of decline in central and peripheral motor conduction. The onset of motor neuron abnormalities was later in B6SJL mice, but progressed more rapidly. Lifespan was longer for B6 than for B6SJL animals. In conclusion, background differences in disease onset and progression are important. The characteristics of the strain should be taken into account in experimental design of therapeutic studies.

Key words::

• Motor neuron disease
• neurodegeneration
• SOD1-G93A mouse
• background
• animal model

Acknowledgments

This work was supported by grant PI071133, TERCEL and CIBERNED funds from the Fondo de Investigación Sanitaria of Spain, grant SAF2009 - 12495 from the Ministerio de Ciencia e Innovación of Spain, FEDER funds, and Action COST-B30 of the EC. We thank Jessica Jaramillo and Marta Morell for technical help. RM is recipient of a predoctoral fellowship from the Ministerio de Educación of Spain.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.