Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory

J. M. Reichel, B. T. Bedenk, N. C. Gassen, K. Hafner, S. A. Bura, S. Almeida-Correa, A. Genewsky, N. Dedic, F. Giesert, A. Agarwal, K. A. Nave, T. Rein, M. Czisch, J. M. Deussing, C. T. Wotjak

Research output: Research - peer-reviewArticle

Abstract

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.

LanguageEnglish (US)
Pages1250-1264
Number of pages15
JournalHippocampus
Volume26
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Galactosidases
Transfection
Hippocampus
Population
Proteins
Bacterial Genes
Lac Operon
Arousal
Neurodegenerative Diseases
Cell Culture Techniques
Neurons
Genes

Keywords

  • cognition
  • hippocampus
  • memory impairment
  • neurodegeneration
  • neurotoxicity
  • transgenic
  • volume loss

ASJC Scopus subject areas

  • Cognitive Neuroscience

Cite this

Reichel, J. M., Bedenk, B. T., Gassen, N. C., Hafner, K., Bura, S. A., Almeida-Correa, S., ... Wotjak, C. T. (2016). Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory. Hippocampus, 26(10), 1250-1264. DOI: 10.1002/hipo.22601

Beware of your Cre-Ation : lacZ expression impairs neuronal integrity and hippocampus-dependent memory. / Reichel, J. M.; Bedenk, B. T.; Gassen, N. C.; Hafner, K.; Bura, S. A.; Almeida-Correa, S.; Genewsky, A.; Dedic, N.; Giesert, F.; Agarwal, A.; Nave, K. A.; Rein, T.; Czisch, M.; Deussing, J. M.; Wotjak, C. T.

In: Hippocampus, Vol. 26, No. 10, 01.10.2016, p. 1250-1264.

Research output: Research - peer-reviewArticle

Reichel, JM, Bedenk, BT, Gassen, NC, Hafner, K, Bura, SA, Almeida-Correa, S, Genewsky, A, Dedic, N, Giesert, F, Agarwal, A, Nave, KA, Rein, T, Czisch, M, Deussing, JM & Wotjak, CT 2016, 'Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory' Hippocampus, vol 26, no. 10, pp. 1250-1264. DOI: 10.1002/hipo.22601
Reichel JM, Bedenk BT, Gassen NC, Hafner K, Bura SA, Almeida-Correa S et al. Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory. Hippocampus. 2016 Oct 1;26(10):1250-1264. Available from, DOI: 10.1002/hipo.22601
Reichel, J. M. ; Bedenk, B. T. ; Gassen, N. C. ; Hafner, K. ; Bura, S. A. ; Almeida-Correa, S. ; Genewsky, A. ; Dedic, N. ; Giesert, F. ; Agarwal, A. ; Nave, K. A. ; Rein, T. ; Czisch, M. ; Deussing, J. M. ; Wotjak, C. T./ Beware of your Cre-Ation : lacZ expression impairs neuronal integrity and hippocampus-dependent memory. In: Hippocampus. 2016 ; Vol. 26, No. 10. pp. 1250-1264
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