A mouse model for spinal muscular atrophy

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

Research output: Contribution to journalArticle

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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

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Spinal Muscular Atrophy
Transgenic Mice
Motor Neuron Disease
Muscle Weakness
Motor Neurons
Exons
Spinal Cord
Skeletal Muscle
Phenotype
Mutation
Genes
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Hsieh, 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

A mouse model for spinal muscular atrophy. / Hsieh, Hsiu Mei; Chang, Jan Gowth; Jong, Yuh Jyh; Wu, Mei Hsiang; Wang, Nancy M.; Tsai, Chang Hai; Li, Hung.

In: Nature Genetics, Vol. 24, No. 1, 21.01.2000, p. 66-70.

Research output: Contribution to journalArticle

Hsieh, HM, Chang, JG, Jong, YJ, Wu, MH, Wang, NM, Tsai, CH & Li, H 2000, 'A mouse model for spinal muscular atrophy', Nature Genetics, vol. 24, no. 1, pp. 66-70. https://doi.org/10.1038/71709
Hsieh HM, Chang JG, Jong YJ, Wu MH, Wang NM, Tsai CH et al. A mouse model for spinal muscular atrophy. Nature Genetics. 2000 Jan 21;24(1):66-70. https://doi.org/10.1038/71709
Hsieh, Hsiu Mei ; Chang, Jan Gowth ; Jong, Yuh Jyh ; Wu, Mei Hsiang ; Wang, Nancy M. ; Tsai, Chang Hai ; Li, Hung. / A mouse model for spinal muscular atrophy. In: Nature Genetics. 2000 ; Vol. 24, No. 1. pp. 66-70.
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