ausblenden:
Schlagwörter:
hippocampus, volume loss, neurodegeneration, neurotoxicity, transgenic , cognition, memory impairment
Zusammenfassung:
Expression of the lacZ-sequence is a widely used reportertool to assess
the transgenic and/or transfection efficacy of a target gene in mice.
Once activated, lacZ is permanently expressed. However, protein
accumulation is one of the hallmarks of neurodegenerative diseases.
Furthermore, the protein product of the bacterial lacZ gene is beta
galactosidase, an analog to the mammalian senescence-associated
beta-galactosidase, a molecular marker for aging. Therefore we studied
the behavioral, structural and molecular consequences of lacZ expression
in distinct neuronal sub-populations. lacZ expression in cortical
glutamatergic neurons resulted in severe impairments in
hippocampus-dependent memory accompanied by marked structural
alterations throughout the CNS. In contrast, GFP expression or the
expression of the ChR2/YFP fusion product in the same cell populations
did not result in either cognitive or structural deficits. GABAergic
lacZ expression caused significantly decreased hyper-arousal and mild
cognitive deficits. Attenuated structural and behavioral consequences of
lacZ expression could also be induced in adulthood, and lacZ
transfection in neuronal cell cultures significantly decreased their
viability. Our findings provide a strong caveat against the use of lacZ
reporter mice for phenotyping studies and point to a particular
sensitivity of the hippocampus formation to detrimental consequences of
lacZ expression. (C) 2016 Wiley Periodicals, Inc.
