A mouse model for spinal muscular atrophy

Hsiu Mei Hsieh-Li, Jan Gowth Chang, Yuh Jyh Jong, Mei Hsiang Wu, Nancy M. Wang, Chang Hai Tsai, Hung Li

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520 Citations (Scopus)

Abstract

The survival motor neuron gene is present in humans in a telomeric copy, SMN1, and several centromeric copies, SMN2. Homozygous mutation of SMN1 is associated with proximal spinal muscular atrophy (SMA), a severe motor neuron disease characterized by early childhood onset of progressive muscle weakness. To understand the functional role of SMN1 in SMA, we produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2, Smn(-/-) mice died during the peri-implantation stage. In contrast, transgenic mice harbouring SMN2 in the Smn(-/-) background showed pathological changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathological changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. Our results demonstrate that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn(-/-) SMN2 mice reflect those seen in SMA patients, providing a mouse model for this disease.

Original languageEnglish
Pages (from-to)66-70
Number of pages5
JournalNature Genetics
Volume24
Issue number1
DOIs
Publication statusPublished - 2000 Jan 21

All Science Journal Classification (ASJC) codes

  • Genetics

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    Hsieh-Li, H. M., Chang, J. G., Jong, Y. J., Wu, M. H., Wang, N. M., Tsai, C. H., & Li, H. (2000). A mouse model for spinal muscular atrophy. Nature Genetics, 24(1), 66-70. https://doi.org/10.1038/71709