Motor alterations are reduced in mice lacking the PARK2 gene in the presence of a human FTDP-17 mutant form of four-repeat tau.
Independent deletion of the PARK2 gene and hTauVLW over-expression in mice produce mild alterations in the brain. However, the presence of both mutations in a parkin-deficient and hTauVLW double mutant mouse causes a tau neuropathology, reactive astrocytosis, and neuronal loss in the cortex and hippocampus, as well as lesions in nigrostriatal and motor neurons. Moreover, these mutants display some memory and exploratory defects that reflect a functional link between parkin and tau proteins. We have tested the motor activity and coordination of these double mutant mice to determine the effects of parkin deletion in mice over-expressing the hTauVLW transgene. While the loss of parkin alone produces increased exploration and alterations in gait and motor coordination, in hTauVLW transgenic mice the absence of parkin causes less prominent motor impairments. These effects suggest the existence of some compensatory mechanisms that are activated when the hTauVLW transgene is over-expressed in the absence of parkin. This mouse model will hopefully help to study the causes of the motor deficits associated with certain neuropathologies related to the tau and parkin proteins, and to find appropriate treatments.
Navarro
P
P
Fundacion Jimenez Diaz-Capio/Clinica Ntra. Sra. Concepción, Universidad Autonoma de Madrid, 28040 Madrid, Spain.
Guerrero
R
R
Gallego
E
E
Avila
J
J
Luquin
R
R
Garcia Ruiz
P J
PJ
Sanchez
M P
MP
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009154:Mutation; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency*; D016875:tau Proteins / Q000235:genetics*
D016875:tau Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein