Abolishing Bax-Dependent Apoptosis Shows Beneficial Effects on Spinal Muscular Atrophy Model Mice

Ming S. Tsai, Yung T. Chiu, Sue H. Wang, Hsiu M. Hsieh-Li, Wei C. Lian, Hung Li

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Spinal muscular atrophy (SMA) is the most common genetic motoneuron degenerative disorder, but the mechanism(s) of motoneuron degeneration is unclear. We previously generated SMA model mice, which genotypically and phenotypically mimicked human SMA patients, by a combination of knockout and transgenic techniques. Here, we used these SMA model mice to decipher the apoptotic mechanism(s) involved in SMA motoneuron degeneration. We found a significant increase in proapoptotic Bax expression in the spinal cords of SMA mice in comparison with their wild-type littermates. After crossing SMA mice with Bax knockout mice, we produced in vivo evidence indicating that Bax protein plays an important role in the degeneration of SMA spinal motoneurons. Progeny Bax-deficient SMA mice showed milder disease severity, longer life spans, and significant increases in spinal motoneuron densities compared to SMA littermates with wild-type Bax genes. Our results strongly suggest that suppression of Bax-involved apoptosis has the potential for amelioration of SMA.

Original languageEnglish
Pages (from-to)1149-1155
Number of pages7
JournalMolecular Therapy
Volume13
Issue number6
DOIs
Publication statusPublished - 2006 Jun 1

Keywords

  • Bax-dependent apoptosis
  • motoneuron degeneration
  • motoneuron diseases
  • spinal muscular atrophy model mice

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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