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Functional behavioral profiling of multiple Cre-driver rat lines.

Asahi Haijima1, Hirohiko Imai2,3, Natsuki Matsushita4

  • 1Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.

Experimental Animals
|January 12, 2026
PubMed
Summary

Cre recombinase expression in rats can alter behavior, impacting locomotor activity and emotional regulation depending on the promoter used. Behavioral validation of Cre-driver lines is crucial for accurate neuroscience research.

Keywords:
Cre-driver ratsCre-loxP systembehavioral phenotypes

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Area of Science:

  • Neuroscience
  • Genetics
  • Behavioral Science

Background:

  • The Cre-loxP system is vital for controlling gene expression in neuroscience research.
  • Concerns exist that Cre recombinase itself may influence brain function and behavior independently of loxP targeting.

Purpose of the Study:

  • To investigate whether Cre recombinase expression, driven by various promoters, affects behavioral phenotypes in rats.
  • To determine if specific Cre-driver rat lines exhibit distinct behavioral alterations.

Main Methods:

  • Evaluated behavioral phenotypes in CAG-Cre, Pvalb-Cre, TH-Cre, Drd2-Cre, Tac1-Cre, and Thy1-Cre rat lines.
  • Utilized behavioral tests including open field, hot plate, prepulse inhibition, and fear conditioning.
  • Conducted structural MRI scans to assess brain morphology.

Main Results:

  • Drd2-Cre rats showed increased locomotor activity and movement speed.
  • CAG-Cre rats displayed altered emotional regulation or learning, evidenced by open field behavior and fear conditioning.
  • No significant changes in nociception or sensorimotor gating were observed across lines.
  • Structural MRI revealed no gross brain abnormalities.

Conclusions:

  • Cre recombinase expression can induce promoter-dependent behavioral changes, particularly affecting emotion and cognition.
  • Behavioral validation of Cre-driver rat lines is essential for reliable interpretation of neuroscience findings.
  • Subtle neural alterations, not gross morphological changes, may underlie observed behavioral effects.