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Behavioral phenotyping of Nestin-Cre mice: implications for genetic mouse models of psychiatric disorders
Sebastian A Giusti1, Claudia A Vercelli2, Annette M Vogl1
1Molecular Neurobiology, Max Planck Institute of Psychiatry, Munich, Germany.
Abstract:
Genetic mouse models based on the Cre-loxP system have been extensively used to explore the influence of specific gene deletions on different aspects of behavioral neurobiology. However, the interpretation of the effects attributed to the gene deletion might be obscured by potential side effects secondary to the Cre recombinase transgene insertion or Cre activity, usually neither controlled nor reported. Here, we performed a comprehensive behavioral analysis of endophenotypes of neuropsychiatric disorders in the extensively used Nestin(Cre) mouse line, commonly employed to restrict genetic modifications to the CNS. We observed no alterations in locomotion, general exploratory activity, learning and memory, sociability, startle response and sensorimotor gating. Although the overall response to stimuli triggering anxiety-like behaviors remained unaltered in Nestin(Cre) mice, a strong impairment in the acquisition of both contextual- and cued-conditioned fear was observed. These results underline the importance of adequately controlling the behavioral performance of the employed Cre-lines per-se in pre-clinical neurobehavioral research.
Insights
The Nestin(Cre) mouse line, used for central nervous system (CNS) research, showed no changes in general behaviors but had impaired fear learning. This highlights the need to assess Cre recombinase activity in genetic studies.
Area of Science:
- Neurobiology
- Behavioral Science
- Genetics
Background:
- Cre-loxP genetic mouse models are vital for studying gene function in neurobiology.
- Potential Cre recombinase activity or transgene insertion can confound results.
- Controlling for Cre-line specific effects is crucial for accurate interpretation.
Purpose of the Study:
- To comprehensively analyze the behavioral endophenotypes of the Nestin(Cre) mouse line.
- To assess potential confounds from Cre recombinase activity in central nervous system (CNS) research.
- To evaluate the behavioral impact of the Nestin(Cre) transgene itself.
Main Methods:
- Utilized a comprehensive battery of behavioral tests in Nestin(Cre) mice.
- Assessed locomotion, exploratory activity, learning and memory, sociability, and sensorimotor gating.
- Evaluated anxiety-like behaviors and conditioned fear acquisition.
Main Results:
- Nestin(Cre) mice exhibited normal locomotion, exploration, learning, memory, sociability, startle response, and sensorimotor gating.
- Anxiety-like behavior acquisition was unaffected.
- Significant impairment in both contextual- and cued-conditioned fear acquisition was observed.
Conclusions:
- The Nestin(Cre) mouse line, while not affecting general behaviors, shows specific deficits in fear learning.
- These findings underscore the necessity of controlling for Cre-line specific behavioral effects in pre-clinical research.
- Researchers must validate Cre-driver lines to ensure accurate attribution of behavioral phenotypes to gene modifications.
