Abnormal social behaviors in mice lacking Fgf17

Gladstone Institute of Neurological Disease, San Francisco, CA 94158-2261, USA.
Genes Brain and Behavior (Impact Factor: 3.66). 05/2008; 7(3):344-54. DOI: 10.1111/j.1601-183X.2007.00357.x
Source: PubMed


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.

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    • "Also, gene-dose could possibly interact in certain models and affect phenotype. One study showed a possible gene-dose effect, reporting less of a decrease in call number in the fibroblast growth factor 17−/− (Fgf17) mouse where heterozygous compared to the homozygous knockout [89] "
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    ABSTRACT: The fmr1 knock out (KO) mouse has been a useful animal model to understand pathology and treatment of FXS, both anatomically and behaviorally. Ultrasonic vocalizations (USVs) are a behavioral tool to assess early life communication deficits in mice. Here, we report on the temporal and spectral features of USVs emitted after maternal separation in wild type (FVB/N) and fmr1 KO pups at postnatal days (P) P4, P7 and P10. The results show changes in the number and duration of calls in fmr1 KO pups and wild type pups were dependent on age and call type. Fmr1 KO pups showed an increased number of USVs at P7 but not at P4 or P10. This increase was specific to Frequency Jump calls. In addition, fmr1 KO mice showed a developmental shift in the temporal distribution of calls, with P10 mice calling in distinct bout patterns. Overall, these findings provide evidence that changes in USV outcomes were specific to certain call types and ages in fmr1 KO mice. Because early postnatal life is a window during which multiple neural systems activate and become established, behavioral measures such as using USVs as a measure of communication, may be useful as a predictor of brain changes and later developmental behavioral changes. Work is needed to better understand the functional outcomes of altered development of USVs and how these changes contribute to later emergence of autistic-like behaviors in animal models of autism.
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    • "Similarly, previous studies in mice and rats have used maternal separation-induced USVs as an early developmental measure of disease (Hodgson et al. 2008; Scattoni et al. 2009; Bowers et al. 2013; Brudzynski 2013). For example, Foxp2 has previously been shown to mediate sex differences in Fibroblast growth factor 17 KO mice, a putative model for schizophrenia has impaired social behavior as well as decreased maternal separation-induced USVs (Scearce-Levie et al. 2008). Moreover, VP plays a role in maternal separation-induced USVs. "
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    Full-text · Article · Oct 2013
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    • "The pattern of normal social habituation but abnormal social novelty response in rcTBI is also distinct from the social recognition impairments recognized in mice lacking oxytocin, estrogen receptors, and vasopressin receptors [28,45,46], and mice socially isolated during adolescence [47], where the experimental mice failed to habituate to the stimulus mouse. However, our findings are similar to those of Fgf17 knockout mice, which have normal social habituation but decreased response to novel stimulus mice [29]. Fgf17 is a fibroblast growth factor that contributes to patterning of the rodent frontal cortex [48]. "
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