Posted 18 April 2004

General Information

Inactivated mouse parkin gene using a pPN2T plasmid with neomycin cassette and two TK gene selection cassettes. In this construction, the Parkin gene was interrupted by the neomycin resistance cassette within exon 3. The first 62 nucleic acids of exon 3 were preserved. The introduced deletion covers an area of 1097 bp, encompassing the last 179 nucleic acids of exon 3 and the first 918 nucleic acids of intron 3. Homologous vector was electroporated into 129SV ES CK35 cells. 2 resulting clones were microinjected into blastocysts from C57/Bl6 mice. Germ line transmission was obtained.

Phenotype

Neuropathological analysis:

Cognitive deficits, inhibition of amphetamine-induced dopamine release and inhibition of glutamate synaptic transmission. The levels of endogenous dopamine are increased in the limbic brain areas of parkin mutant mice and there is a shift towards increased metabolism of dopamine by MAO. There was no evidence of loss of nigrostriatal dopamine neurons. However, the level of dopamine transporter protein was reduced in these animals.

Behavioral:

The parkin mutant mice are viable and reproduce successfully, but display abnormal baseline motor activity. Also display decreased body weight and temperature.

Availability

Thomas A. Rooney
Aventis Pharma SA
13 Quai Jules Guesde, F-94400
Vitry-sur-Seine, France
Telephone: 33 158932645
Email: thomas.rooney@aventis.com

Reference

Primary:

Itier JM, Ibanez P, Mena MA, et al. Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum Mol Genet 2003; 12: 2277-2291 Abstract