X11-like protein deficiency is associated with impaired conflict resolution in mice.
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.
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
Yoshitake
Y
Sano
Veravej G
VG
Ornthanalai
Kazuyuki
K
Yamada
Chihiro
C
Homma
Hitomi
H
Suzuki
Toshiharu
T
Suzuki
Niall P
NP
Murphy
Shigeyoshi
S
Itohara
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000223:Adaptation, Psychological / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism; D001835:Body Weight / Q000235:genetics; D015820:Cadherins / Q000172:deficiency*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D002352:Carrier Proteins; D003163:Competitive Behavior / Q000502:physiology*; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000235:genetics; D005106:Exploratory Behavior / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D005697:Galactosides / Q000378:metabolism; D018737:Hand Strength / Q000502:physiology; D007036:Hypothermia, Induced; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D019913:Nuclear Localization Signals / Q000235:genetics; D016548:Prosencephalon / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D018709:Statistics, Nonparametric; D013997:Time Factors
C491635:Apba2 protein, mouse; D015306:Biogenic Monoamines; D015820:Cadherins; D002352:Carrier Proteins; D005697:Galactosides; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; C007816:beta-galactoside; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D004317:Doxorubicin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517671:Camk2a protein, mouse