Drugs Discovery Assets:

Animal Models

SMA Foundation

Animal models are key to translational research. They are needed for identifying and evaluating potential therapeutics that may ultimately be effective in SMA patients. Since 2003, the SMA Foundation has spent over $27M on animal models through generating new SMA mouse models, making them available to the research community,  and establishing an in vivo drug efficacy testing platform.

Multiple mouse models of SMA have been produced, generally by knocking out the endogenous mouse SMN1 gene and replacing it with one or more copies of the human SMN2 gene that produces much less full-length SMN protein than the SMN1 gene. Many of the most commonly used mouse models by SMA researchers, including the delta7 mouse (Le et al., 2005), present severe motor deficits, and generally die before 14 days of age. In 2006, the Foundation entered into an agreement with Regeneron Pharmaceuticals to develop a series of mice that would better model milder forms of SMA. A summary of the SMA Foundation’s SMA allelic series of mice is available below.

The SMA Foundation has partnered with the The Jackson Laboratory (JAX) to support the importation of key mouse models of SMA into the JAX mouse repository. To date, approximately 40 SMA-related mouse lines are available for order at JAX.

Line Hybrid SMN1 Copies SMN2 Copies Phenotype Jax Stock # BL6 Jax Stock # FVB
A/A 0 0 Embryonic lethal 7963 7955
A/B 1 0 Embryonic lethal    
A/C 1 1 Embryonic lethal    
A/D 1 3 Viable    
B/B 2 0 Embryonic lethal 8453 8713
B/C 2 1 Embryonic lethal    
B/D 2 3 Viable    
C/C 2 2 Viable, necrosis 8714 8604
C/D 2 4 Viable    
D/D 2 6 Viable 9378 9391

Table 1. SMA Allelic Series Mice Available at The Jackson Laboratory (JAX). Mice listed with JAX stock numbers are available for ordering in either congenic C57/Bl6 or FVBnj strain backgrounds. Generally, increased copy numbers of SMN rescue the survival phenotype of mice with SMN deficiencies. The C/C mice are the homozygous line with the fewest number of human SMN2 genes that is viable. The SMA Foundation and their collaborators have developed further information on the phenotypes of this animal. Please contact researchtools@smafoundation.org for more information on the C/C mouse and other SMA Foundation allelic series mice.