Details

Autor(en) / Beteiligte

• Sgadò, Paola
• Albéri, Lavinia
• Gherbassi, Daniel
• Galasso, Sherri L.
• Ramakers, Geert M. J.
• Alavian, Kambiz N.
• Smidt, Marten P.
• Dyck, Richard H.
• Simon, Horst H.

Titel

Slow Progressive Degeneration of Nigral Dopaminergic Neurons in Postnatal Engrailed Mutant Mice

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2006-10, Vol.103 (41), p.15242-15247

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• The homeobox transcription factors Engrailed-1 and Engrailed-2 are required for the survival of mesencephalic dopaminergic neurons in a cell-autonomous and gene-dose-dependent manner. Because of this requirement, the cells die by apoptosis when all four alleles of the Engrailed genes are genetically ablated (En1-/-; En2-/-). In the present study, we show that viable and fertile mice, heterozygous null for Engrailed-1 and homozygous null for Engrailed-2 (Enf+/-;En2-/-), have an adult phenotype that resembles key pathological features of Parkinson's disease. Specifically, postnatal mutant mice exhibit a progressive degeneration of dopaminergic neurons in the substantia nigra during the first 3 mo of their lives, leading to diminished storage and release of dopamine in the caudate putamen, motor deficits similar to akinesia and bradykinesia, and a lower body weight. This genetic model may provide access to the molecular etiology for Parkinson's disease and could assist in the development of novel treatments for this neurodegenerative disorder.