title: Abolishing Trp53-dependent apoptosis does not benefit spinal muscular atrophy model mice.
abstract: Spinal muscular atrophy (SMA) is the most common genetic motoneuron degenerative disorder, but the mechanism(s) of motoneuron death is unclear. Previously, a direct interaction between tumor-suppressive TP53 protein and the SMA determinant gene product, survival motor neuron protein, was identified and therefore it has been suggested that a mechanism of TP53-dependent apoptosis plays an important role in motoneuron degeneration in SMA. We used our SMA model mice, generated by a combination of knockout and transgenic techniques, to decipher the role of TP53 protein in the motoneuron degeneration in SMA. We detected a significant increase of Trp53 expression in the spinal cord of SMA-like mice compared to their normal littermates. After crossing SMA-like mice with Trp53 knockout mice, the progeny Trp53-deficient SMA-like mice did not show milder disease severity or longer lifespan compared to SMA littermates with wild-type Trp53 genes. Our studies provide in vivo evidence indicating that Trp53-dependent apoptosis does not play a crucial role in motoneuron degeneration in SMA-like mice. European Journal of Human Genetics (2006) 14, 372-375. doi:10.1038/sj.ejhg.5201556; published online 4 January 2006.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Ming Shiun
authors.initials: MS
authors.lastname: Tsai
authors.forename: Yung Tsung
authors.initials: YT
authors.lastname: Chiu
authors.forename: Sue Hong
authors.initials: SH
authors.lastname: Wang
authors.forename: Hsiu Mei
authors.initials: HM
authors.lastname: Hsieh-Li
authors.forename: Hung
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D016158:Genes, p53; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000473:pathology; D010641:Phenotype; D013116:Spinal Cord / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53