Abnormal social behaviors in mice lacking Fgf17.
The fibroblast growth factor family of secreted signaling molecules is essential for patterning in the central nervous system. Fibroblast growth factor 17 (Fgf17) has been shown to contribute to regionalization of the rodent frontal cortex. To determine how Fgf17 signaling modulates behavior, both during development and in adulthood, we studied mice lacking one or two copies of the Fgf17 gene. Fgf17-deficient mice showed no abnormalities in overall physical growth, activity level, exploration, anxiety-like behaviors, motor co-ordination, motor learning, acoustic startle, prepulse inhibition, feeding, fear conditioning, aggression and olfactory exploration. However, they displayed striking deficits in several behaviors involving specific social interactions. Fgf17-deficient pups vocalized less than wild-type controls when separated from their mother and siblings. Elimination of Fgf17 also decreased the interaction of adult males with a novel ovariectomized female in a social recognition test and reduced the amount of time opposite-sex pairs spent engaged in prolonged, affiliative interactions during exploration of a novel environment. After social exploration of a novel environment, Fgf17-deficient mice showed less activation of the immediate-early gene Fos in the frontal cortex than wild-type controls. Our findings show that Fgf17 is required for several complex social behaviors and suggest that disturbances in Fgf17 signaling may contribute to neuropsychiatric diseases that affect such behaviors.
Scearce-Levie
K
K
Gladstone Institute of Neurological Disease, San Francisco, CA 94158-2261, USA. kscearce-levie@gladstone.ucsf.edu
Roberson
E D
ED
Gerstein
H
H
Cholfin
J A
JA
Mandiyan
V S
VS
Shah
N M
NM
Rubenstein
J L R
JL
Mucke
L
L
D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D005346:Fibroblast Growth Factors / Q000172:deficiency*; D005625:Frontal Lobe / Q000502:physiology / Q000503:physiopathology; D005786:Gene Expression Regulation; D016762:Genes, fos; D006185:Habituation, Psychophysiologic; D007858:Learning / Q000502:physiology; D008297:Male; D008425:Maternal Behavior; D001523:Mental Disorders / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D021641:Recognition, Psychology; D012919:Social Behavior
C484726:Fgf17 protein, mouse; D005346:Fibroblast Growth Factors