Posted 17 February 2004

General Information

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.

Phenotype

Neuropathological analysis:

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.

Behavioral:

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.

Availability

Jie Shen
Center for Neurologic Diseases, Harvard Institutes of Medicine
77 Avenue Louis Pasteur
Boston, MA 02115
Tel.: 617-525-5561
Fax: 617-525-5522
jshen@rics.bwh.harvard.edu

Reference

Primary:

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. Abstract