Impaired fear response in mice lacking GIT1.
G protein-coupled receptor kinase interacting protein 1 (GIT1) belongs to the family of Arf GAP proteins and has been implicated in the regulation of G protein-coupled receptor (GPCR) sequestration, cell migration, synapse formation and dendritic spine morphogenesis in neurons. To extend these cellular studies on GIT1 to an in vivo system, we generated mice with globally inactivated Git1 gene by breeding mice carrying a conditional Git1(flox) allele with mice expressing the CMV-Cre transgene. Although many GIT1 knockout (GIT1-KO) animals died shortly after birth, homozygous mutants that survived the early post-partum period developed normally into adulthood and were fertile. Behavioral analyses of adult GIT1-KO mice revealed normal exploratory, anxiety- and depressive-like behaviors. However, GIT1-KO mice show impaired responses to fear conditioning and fear-potentiated startle. Overall, these findings suggest that GIT1 is involved in the regulation of amygdala-mediated experience-based emotional behaviors.
Schmalzigaug
Robert
R
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Rodriguiz
Ramona M
RM
Bonner
Pamela E
PE
Davidson
Collin E
CE
Wetsel
William C
WC
Premont
Richard T
RT
D000161:Acoustic Stimulation / Q000009:adverse effects; D000221:Adaptation, Ocular / Q000235:genetics; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D018797:Cell Cycle Proteins; D003214:Conditioning, Classical; D004167:Diphtheria Toxin / Q000378:metabolism; D004597:Electroshock / Q000009:adverse effects; D005239:Fear / Q000502:physiology*; D005260:Female; D020690:GTPase-Activating Proteins / Q000172:deficiency*; D008297:Male; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D019964:Mood Disorders / Q000235:genetics* / Q000503:physiopathology*; D009355:Neomycin / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism; D013997:Time Factors
D018797:Cell Cycle Proteins; D004167:Diphtheria Toxin; D020690:GTPase-Activating Proteins; C120766:Git1 protein, mouse; D013937:Thymidine Kinase; D009355:Neomycin