28 June 2002. A new mouse model of Parkinson's published in the current early online edition of PNAS develops a particularly severe motor disorder similar to Parkinson's disease but, as with a similar model reported last month, no degeneration of substantia nigra neurons (see related news item).
Michael Lee and colleagues at Johns Hopkins University in Baltimore, Maryland, and at the National Cancer Institute in Frederick, Maryland, created a mouse carrying the human gene encoding a mutation in α-synuclein, as done by Giasson and colleagues. The A53T mutation causes a familial form of PD. As with the previous report, this mouse develops insoluble aggregates containing α-synuclein that are reminiscent of the Lewy bodies of PD and other α-synucleinopathies, such as dementia with Lewy bodies and multiple systems atrophy. There was also glial evidence of neurodegeneration in motor areas of the brain, which was manifested in a progressive motor disorder that lead to early death.
Yet both these models fail to reproduce loss of dopamine neurons in the substantia nigra, the hallmark of PD. Lee and colleagues suggests that rodent SN neurons may be more resistant to α-synuclein-induced neurodegeneration, an idea that has support from in vitro and other transgenic studies.-Hakon Heimer.
Lee MK, Stirling W, Xu Y, Xu X, Qui D, Mandir AS, Dawson TM, Copeland NG, Jenkins NA, Price DL. Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53 > Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8968-73. Abstract