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Open Access Green as soon as Postprint is submitted to ZB.
Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory.
Hippocampus 26, 1250-1264 (2016)
Expression of the lacZ-sequence is a widely used reporter-tool 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 ß-galactosidase, an analog to the mammalian senescence-associated ß-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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cognition ; Hippocampus ; Memory Impairment ; Neurodegeneration ; Neurotoxicity ; Transgenic ; Volume Loss; Site-specific Recombination; Beta-galactosidase Activity; Embryonic Stem-cells; Transgenic Mice; Alzheimers-disease; Gene-expression; Mouse Models; Targeted Disruption; Principal Neurons; Conditioned Fear
ISSN (print) / ISBN
1050-9631
e-ISSN
1098-1063
Journal
Hippocampus
Quellenangaben
Volume: 26,
Issue: 10,
Pages: 1250-1264
Publisher
Wiley
Publishing Place
Hoboken
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)