Spinal muscular atrophy (SMA), the second most common fatal, autosomal recessive disease of infants, manifests as generalized muscle weakness. The most severe form (Type I, Werdnig-Hoffmann disease) is associated with quadriplegia, respiratory muscle paralysis and death in infancy. Less severe forms are classified as Type II and Type III, based on age of onset and ultimate motor disability. Some spinal motor neurons show chromatolysis and the number of these cells is decreased. Recently, SMA has been mapped to chromosome 5q11.2-13.3, a region that contains three candidate genes: Survival Motor Neuron (SMN); Neuronal Apoptosis Inhibitory Protein (NAP); and p44, a subunit of transcription factor II H (TFIIH). Homozygous deletions or deleterious mutations in SMN are present in all SMA patients, and in some affected individuals, deletions have been identified in one or both of the other genes. These extensive deletions may be associated with a more severe phenotype. We have identified and characterized the mouse homologue of SMN, MoSMN, which is 82% identical to SMN at the amino-acid level. Unlike the duplicated human SMN, MoSMN is present in single copy. Like its human counterpart, MoSMN is ubiquitously expressed, but unlike SMN, MoSMN does not appear to be alternatively spliced. In-situ hybridization analysis of the mouse nervous system revealed that MoSMN mRNA is expressed in spinal cord and throughout the brain, with relatively higher levels of expression in the hippocampus and cerebellum.
Bibliographical noteFunding Information:
We wish to thank Thomas O. Crawford (Johns Hopkins) for helpful discussions, Ty Lanahan (Johns Hopkins) for the embryonic mouse brain cDNA library, and Hilda H. Slunt for technical assistance. AB was supported by a Neurological Sciences Academic Development Award (K12 NSO1691), DLP is the recipient of a Javitz Neuroscience Investigator Award (NIH NS 10580), DLP and SSS are supported by an NIH grant AG 05146, BAR was supported by grants from the National Institutes of Health (KO8NS01781), and the Muscular Dystrophy Association, and MKL was supported by the Amyotrophic Lateral Sclerosis Association.
- Motor neuron disease
- Mouse survival motor neuron gene
- Spinal muscular atrophy
- Survival motor neuron