JAX Mice for spinal muscular atrophy research

Spinal muscular atrophy (SMA)

SMA is the leading genetic cause of infant and toddler death. An autosomal recessive disease, it is caused by a faulty gene on Chromosome 5, leading to loss of motor neurons in the spinal cord and inability to control voluntary muscle movements. Affected children are weak, cry feebly, and have trouble swallowing, sucking, and breathing. Onset occurs from before birth to six months. From 25,000 to 55,000 people suffer from SMA in the United States, Europe and Japan (Spinal Muscular Atrophy Foundation, www.smafoundation.org). The National Institute of Neurological Disorders and Stroke selected SMA as the prototype for a $22 million translational research project expected to yield drug candidates for Investigational New Drug Application filing within three to five years.

View our print-friendly mouse model list (pdf)

JAX^® Mice Models

The Jackson Laboratory received support from the SMA Foundation to make available the first group of mouse models for SMA. The mice will be available to the scientific community in the first half of 2005. Three of the new models were donated by Dr. Arthur Burghes of Ohio State University, and the fourth by Dr. Hung Li of the Institute of Molecular Biology in Taipei. Each of the models include a targeted mutation of the endogenous mouse survival motor neuron (Smn) gene, combined with transgenes involving various forms of human SMN2 and/or SMN1. The donated models are:

*FVB.Cg-Tg(SMN2delta7)4299Ahmb Tg(SMN2)89Ahmb Smn1^tm1Msd/J**	Stock Number 005025
*FVB.Cg-Tg(SMN2)89Ahmb Tg(SMN1A2G)2023Ahmb Smn1^tm1Msd/J**	Stock Number 005026
*FVB.Cg-Tg(SMN2)89Ahmb Smn^tm1Msd/J*	Stock Number 005024
*FVB.Cg-Tg(SMN2)2Hung Smn1^tm1Hung/J*	Stock Number 005058

Please see the strain data sheets for licensing information.

The latter two are briefly described below.

**FVB.Cg-Tg(SMN2)89Ahmb Smn^tm1Msd/J** (Stock Number 005024)

Mice homozygous for the targeted mutant Smn1 allele and that carry the SMN2 transgene exhibit symptoms and neuropathology similar to humans with type I proximal spinal muscular atrophy (SMA). These mutants are either stillborn or survive for only 4–6 days. Mice dying shortly after birth are slightly smaller (1.33 g. vs. 1.51 g.) than normal littermates. Those surviving for several days are indistinguishable from normal littermates in the first 48 hours, after which they tremble and have difficulty suckling, moving, and breathing. At death, they are noticeably smaller than normal littermates (1.47 g vs. 4.59). They have a bell-shaped trunk, presumably from intercostal muscle weakness, a characteristic of type I SMA. Homozygotes bearing the Smn targeted mutation without a copy of the SMN2 transgene die embryonically.

Reference

Monani UR, Sendtner M, Coovert DD, Parsons DW, Andreassi C, Le TT, Jablonka S, Schrank B, Rossol W, Prior TW, Morris GE, Burghes AH. 2000. The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy. Hum Mol Genet 9:333-9.

**FVB.Cg-Tg(SMN2)2Hung Smn1^tm1Hung/J** (Stock Number 005058)

Mice homozygous for the Smn targeted mutation and hemizygous for the SMN2 transgene are viable, fertile, and have short thickened tails. RT-PCR analysis detects alternative splicing of the transgene. Histological examination of tail tissue reveals atrophic muscles and subcutaneous edema. Skeletal muscle tissue has fewer myocytes and atrophic muscle bundles. Large motor neurons in the anterior horns of the spinal cord degenerate and are lost. There is a strong correlation between estimated copy number of the transgene and severity of the phenotype. These mice exhibit a molecular and progressive neurodegenerative phenotype similar to Type III spinal muscular atrophy. Mice homozygous for the targeted mutation and that do not carry the transgene before embryonic day 6.5.

Reference

Hsieh-Li HM, Chang JG, Jong YJ, Wu MH, Wang NM, Tsai CH, Li H. 2000. A mouse model for spinal muscular atrophy. Nat Genet 24:66-70.