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.
Sano
Yoshitake
Y
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
Ornthanalai
Veravej G
VG
Yamada
Kazuyuki
K
Homma
Chihiro
C
Suzuki
Hitomi
H
Suzuki
Toshiharu
T
Murphy
Niall P
NP
Itohara
Shigeyoshi
S
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