Park2-null/tau transgenic mice reveal a functional relationship between parkin and tau.
Mutations, haplotypes, and polymorphisms of tau and Park-2 genes constitute risk factors for developing tauopathies. In order to analyze the possible relationship between parkin and tau we generated a double-mutant mouse deficient for Park-2 expression and overexpressing a mutant tau protein (hTauVLW). Mice develop normally, although the median survival rate is considerably reduced with respect to wild type (45%). Aggregates of phosphorylated tau in neurons and reactive gliosis are quite abundant in cortex and hippocampus of these mice. Moreover, while in young transgenic mice the hTauVLW immunostained transgene product is observed in both cell bodies and dendrites, the hTauVLW mutant protein is only detected in the neuronal cell bodies when Park-2 gene is additionally deleted. Moreover, DNA fragmentation was detected by the TUNEL method, and cerebral atrophy is also present in these regions. The levels of phosphorylated tau and Hsp70 are increased in the double-mutant mice, while CHIP expression in hippocampus is lower when the Park-2 gene is deleted. Thus, the combination of Park-2 gene deletion with hTauVLW transgene overexpression in mice produces serious neuropathological effects, which reflect the existence of some relationship between both proteins.
Guerrero
Rosa
R
Fundacion Jimenez Diaz-Capio/Clinica Ntra. Sra. Concepcion, Universidad Autonoma de Madrid, 28040 Madrid, Spain.
Navarro
Paloma
P
Gallego
Eva
E
Avila
Jesus
J
de Yebenes
Justo G
JG
Sanchez
Marina P
MP
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D017353:Gene Deletion; D005911:Gliosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008215:Lymphocytes, Null / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
D000906:Antibodies; D050505:Mutant Proteins; D016875:tau Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein