research report      name index      key word index      corresp.unit            Page in german      Imprint + Privacy Policy   

Third-party-funded project

Title:
The Human centromeric Survival Motor Neuron (SMN2) gene rescues embryonic lethality in Smn-/- mice and results in a mouse with Spinal Muscular Atrophy

Project management at the University of Würzburg:

• Prof. Dr. med. Michael Sendtner ,Tel: 201-49767,Fax: 201-49788,Mail: sendtner@mail.uni-wuerzburg.de

Participating scientists:

• Dr. rer. nat. Sibylle Jablonka

Abstract:
Spinal Muscular Atrophy is caused by deletion of one of two smn genes which are located on human chromosome 5. The human smn2 gene which is preserved in Spinal Muscular Atrophy, gives ?raise to a truncated protein, but also, to a low level, to full length smn gene product. We have investigated the effect of smn gene dose reduction in smn heterocygous mice and in mice in which the human smn2 gene was expressed as a transgene on a smn-/- background. Those mouse models revealed postnatal loss of motoneurons and thus resemble the human disease. Our data also indicate that high expression of smn2 can prevent disease, by this way pointing the way to new therapeutic strategies for Spinal Muscular Atrophy.

Key words:
    Cell death

Projekt period: from 01.1996 to 12.2000

Funding institution:
DFG ( To 61/8-3 und 61/8-4 ) ,Granting date: 07.07.1997
Landeshaushalt Wissenschaftsministerium

Preceding project:
DFG To 61/-1

Publications:

• Jablonka et al.. (2000). The role of SMN in spinal muscular atrophy. (monograph)
• Schrank et al.. (1997). Inactivation of the survival motor neruon gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. PNAS 94, (scientific article)
• Jablonka et al.. (2000). Reduced survival motor neuron (SMN) gene dose in mice leads to motor neuron degeneration: an animal model for spinal muscular atrophy type III. Hum Mol Genet, (scientific article)

Links:
Institute for Clinical Neurobiology