Behavioral phenotyping of Nestin-Cre mice: implications for genetic mouse models of psychiatric disorders.
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.
Molecular Neurobiology, Max Planck Institute of Psychiatry, Munich, Germany.
Sebastian A
SA
Giusti
Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina.
Claudia A
CA
Vercelli
Molecular Neurobiology, Max Planck Institute of Psychiatry, Munich, Germany.
Annette M
AM
Vogl
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
Adam W
AW
Kolarz
Molecular Neurobiology, Max Planck Institute of Psychiatry, Munich, Germany.
Natalia S
NS
Pino
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
Jan M
JM
Deussing
Molecular Neurobiology, Max Planck Institute of Psychiatry, Munich, Germany. Electronic address: refojo@mpipsykl.mpg.de.
Damian
D
Refojo
D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D058068:Endophenotypes; D005106:Exploratory Behavior; D005239:Fear; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007858:Learning; D008297:Male; D008568:Memory; D001523:Mental Disorders / Q000235:genetics / Q000523:psychology*; D008822:Mice, Transgenic; D009043:Motor Activity; D064231:Nestin / Q000235:genetics; D009483:Neuropsychological Tests; D013216:Reflex, Startle; D055139:Sensory Gating; D012919:Social Behavior
C577485:Nes protein, mouse; D064231:Nestin; C045073:Cre recombinase; D019426:Integrases
Anxiety; Cre-loxP system; Fear conditioning; Mouse model; Nestin(Cre)