Spinal Muscular Atrophy Efficacy Studies

Spinal Muscular Atrophy (SMA) Types I, II and III cause weakness and wasting of the voluntary muscles in the arms and legs of infants and children. The disorders are caused by an abnormal or missing gene known as the survival motor neuron 1 (SMN1), which is responsible for the production of a protein essential to the survival of lower motor neurons in the spinal cord. SMN2 is a human-specific duplication of the SMN1 gene that only partially complements the loss of SMN1.

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SMA Efficacy Studies

Efficacy studies performed by JAX® In Vivo Services for SMA include various in-life measurements:  body weights, survival, righting reflex, echocardiography (ECG) and electrophysiology, as well as assessment of neuromuscular junction maturation, tissue/blood collection, and increases in SMN as measured by ELISA.

  • SMA-like:  FVB.Cg-Smn1tm1HungTg(SMN2)2Hung/J (005058).  These mice lack the murine Smn1 gene and carry the human SMN2 transgene. They exhibit a rapid neurodegenerative phenotype similar to Type I/II SMA.
  • Smn1C: FVB.129(B6)-Smn1tm5(Smn1/SMN2)Mrph/J (008604).  The Smn1C hybrid allele contains two Smn1/SMN2 hybrid genes in tandem. In addition to the simplicity of the genetics, this mouse model is one of the only license-free SMA models.  Like strain 005058, it carries a full length copy of the human SMN2 gene, and  is therefore particularly useful in initial testing of SMN2-inducing compounds for target engagement.  Outcome measurements include standard ELISA assays for SMN but these mice also provide a built in barometer for increased SMN levels as determined by tail length and alleviation of necrosis.
  • FVB.Cg-Grm7Tg(SMN2)89Ahmb Smn1tm1Msd Tg(SMN2*delta7)4299Ahmb/J (005025) mice, commonly referred to as D7 or delta 7, are homozygous for the Smn1 targeted mutant allele and homozygous for two human transgenes.  Triple mutant mice model the severe form of the disease and are most often used in efficacy studies associated with early intervention due their shortened life span.