Memory and exploratory impairment in mice that lack the Park-2 gene and that over-express the human FTDP-17 mutant Tau.
While mutations in the Park-2 gene are the most frequent cause of autosomal-recessive juvenile parkinsonism (AR-JP), they are also present in several forms of tauopathies. Conversely, in some forms of parkinsonism, mutations in the tau gene have also been observed. Deletion of the Park-2 gene and over-expression of mutant tau independently produce mild brain alterations in mice. However, the presence of both mutations simultaneously causes a tau neuropathology, involving reactive astrocytosis, neuron loss in the cortex and hippocampus, and lesions in nigrostriatal and motor neurons. Furthermore, mutant tau over-expression in mice produces important memory impairment. When "parkin" function was abolished in young tau transgenic mice, the memory alterations were exaggerated. Moreover, additional exploratory and motor deficits were observed in older mice, causing the memory alterations to be underestimated. Thus, while memory deficits are more severe in young mice they were somehow attenuated by exploratory impairments in ageing mutants. This double mutant animal will serve as a useful experimental tool to investigate the abnormal processing of hyperphosphorylated tau and its relationship to the development of the cognitive deficits associated with certain neurodegenerative diseases.
Navarro
Paloma
P
Fundacion Jimenez Diaz-Capio/Clinica Ntra Sra Concepcion, Universidad Autonoma de Madrid, Madrid, Spain.
Guerrero
Rosa
R
Gallego
Eva
E
Avila
Jesus
J
Luquin
Rosario
R
Ruiz
Pedro J Garcia
PJ
Sanchez
Marina P
MP
D000367:Age Factors; D000818:Animals; D005106:Exploratory Behavior / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D011597:Psychomotor Performance / Q000502:physiology; D021641:Recognition, Psychology / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D050505:Mutant Proteins; D016875:tau Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein