X11-like protein deficiency is associated with impaired conflict resolution in mice

J Neurosci. 2009 May 6;29(18):5884-96. doi: 10.1523/JNEUROSCI.5756-08.2009.

Abstract

Understanding how emotion is generated, how conflicting emotions are regulated, and how emotional states relate to sophisticated behaviors is a crucial challenge in brain research. Model animals showing selective emotion-related phenotypes are highly useful for examining these issues. Here, we describe a novel mouse model that withdraws in approach-avoidance conflicts. X11-like (X11L)/Mint2 is a neuronal adapter protein with multiple protein-protein interaction domains that interacts with several proteins involved in modulating neuronal activity. X11L-knock-out (KO) mice were subordinate under competitive feeding conditions. X11L-KO mice lost significantly more weight than cohoused wild-type mice without signs of decreased motivation to eat or physical weakness. In a resident-intruder test, X11L-KO mice showed decreased intruder exploration behavior. Moreover, X11L-KO mice displayed decreased marble-burying, digging and burrowing behaviors, indicating aberrant ethological responses to attractive stimuli. In contrast, X11L-KO mice were indistinguishable from wild-type mice in the open field, elevated plus maze, and light/dark transition tests, which are often used to assess anxiety-like behavior. Neurochemical analysis revealed a monoamine imbalance in several forebrain regions. The defective ethological responses and social behaviors in X11L-KO mice were rescued by the expression of X11L under a Camk2a promoter using the Tet-OFF system during development. These findings suggest that X11L is involved in the development of neuronal circuits that contribute to conflict resolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Adaptation, Psychological / physiology
  • Analysis of Variance
  • Animals
  • Anxiety / genetics
  • Avoidance Learning / physiology*
  • Behavior, Animal / physiology
  • Biogenic Monoamines / metabolism
  • Body Weight / genetics
  • Cadherins / deficiency*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Carrier Proteins
  • Competitive Behavior / physiology*
  • Conflict, Psychological*
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology
  • Drinking Behavior / drug effects
  • Drinking Behavior / physiology
  • Eating / genetics
  • Exploratory Behavior / physiology
  • Feeding Behavior / physiology
  • Galactosides / metabolism
  • Hand Strength / physiology
  • Hypothermia, Induced
  • Interpersonal Relations
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Activity / genetics
  • Nerve Tissue Proteins / deficiency*
  • Nuclear Localization Signals / genetics
  • Prosencephalon / metabolism
  • Protein Interaction Domains and Motifs
  • Statistics, Nonparametric
  • Time Factors

Substances

  • Apba2 protein, mouse
  • Biogenic Monoamines
  • Cadherins
  • Carrier Proteins
  • Galactosides
  • Nerve Tissue Proteins
  • Nuclear Localization Signals
  • beta-galactoside
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Doxorubicin
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Camk2a protein, mouse