Posted 17 February 2004
A targeting vector was constructed in which most of exon 3 was replaced in-frame
by the coding sequence of EGFP, followed by translation and transcription termination
sequences and the PGK-neo cassette. Vector was transfected into J1 (129/Sv)
ES cells. Resulting clones were injected into C57BL/6 and Balb/c blastocysts. Chimeric
offspring were crossed with C57BL/6 or 129/Sv mice to obtain germline transmission.
Exhibit grossly normal brain morphology. Exhibit a significant increase in extracellular
dopamine concentration in the striatum. Reduced synaptic excitability of medium-sized
spiny striatal neurons. The number of dopaminergic neurons in the substantia nigra
is normal up to the age of 24 months.
Parkin-/- mice are viable and fertile without obvious abnormalities. No
significant alterations in their general behavior and exploratory anxiety. But exhibit
deficits in behavioral tasks sensitive to dysfunction of the nigrostriatal pathway.
Center for Neurologic Diseases, Harvard Institutes of Medicine
77 Avenue Louis Pasteur
Boston, MA 02115
Goldberg MS, Fleming SM, Palacino JJ, et al. Parkin-deficient mice exhibit nigrostriatal
deficits but not loss of dopaminergic neurons. J Biol Chem 2003; 278: 43628-43635.