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Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos.

TitleInactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos.
Publication TypeJournal Article
Year of Publication1997
AuthorsSchrank B, Götz R, Gunnersen JM, Ure JM, Toyka KV, Smith AG, Sendtner M
JournalProc Natl Acad Sci U S A
Volume94
Issue18
Pagination9920-5
Date Published1997 Sep 2
ISSN0027-8424
KeywordsAmino Acid Sequence, Animals, Cell Death, Cyclic AMP Response Element-Binding Protein, Embryonic and Fetal Development, Gene Expression Regulation, Developmental, Humans, Mice, Mice, Knockout, Molecular Sequence Data, Motor Neurons, Nerve Tissue Proteins, RNA-Binding Proteins, SMN Complex Proteins
Abstract

Proximal spinal muscular atrophy is an autosomal recessive human disease of spinal motor neurons leading to muscular weakness with onset predominantly in infancy and childhood. With an estimated heterozygote frequency of 1/40 it is the most common monogenic disorder lethal to infants; milder forms represent the second most common pediatric neuromuscular disorder. Two candidate genes-survival motor neuron (SMN) and neuronal apoptosis inhibitory protein have been identified on chromosome 5q13 by positional cloning. However, the functional impact of these genes and the mechanism leading to a degeneration of motor neurons remain to be defined. To analyze the role of the SMN gene product in vivo we generated SMN-deficient mice. In contrast to the human genome, which contains two copies, the mouse genome contains only one SMN gene. Mice with homozygous SMN disruption display massive cell death during early embryonic development, indicating that the SMN gene product is necessary for cellular survival and function.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID9275227
PubMed Central IDPMC23295