Behavioral abnormalities in the Fmr1-KO2 mouse model of fragile X syndrome: The relevance of early life phases

Julie Gaudissard, Melanie Ginger, Marika Premoli, Maurizio Memo, Andreas Frick, Susanna Pietropaolo
Autism Research. 2017-06-07; 10(10): 1584-1596
DOI: 10.1002/aur.1814

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Gaudissard J(1)(2), Ginger M(3)(4), Premoli M(5), Memo M(5), Frick A(3)(4), Pietropaolo S(1)(2).

Author information:
(1)University of Bordeaux, INCIA, Pessac, France.
(2)CNRS, INCIA, UMR 5287, Pessac, France.
(3)INSERM, Neurocentre Magendie, U1215, Bordeaux, France.
(4)University of Bordeaux, Neurocentre Magendie, U1215, Bordeaux, France.
(5)Department of Molecular and Translational Medicine, University of Brescia,
Brescia, Italy.

Fragile X syndrome (FXS) is a developmental disorder caused by a mutation in the
X-linked FMR1 gene, coding for the FMRP protein which is largely involved in
synaptic function. FXS patients present several behavioral abnormalities,
including hyperactivity, anxiety, sensory hyper-responsiveness, and cognitive
deficits. Autistic symptoms, e.g., altered social interaction and communication,
are also often observed: FXS is indeed the most common monogenic cause of
autism. Mouse models of FXS are therefore of great interest for research on both
FXS and autistic pathologies. The Fmr1-KO2 mouse line is the most recent FXS
model, widely used for brain studies; surprisingly, little is known about the
face validity of this model, i.e., its FXS-like behavioral phenotype.
Furthermore, no data are available for the age-related expression of the
pathological phenotypes in this mouse line, a critical issue for modelling
neurodevelopmental disorders. Here we performed an extensive behavioral
characterization of the KO2 model at infancy, adolescent and adult ages.
Hyperactivity, altered emotionality, sensory hyper-responsiveness and memory
deficits were already present in KO mice at adolescence and remained evident at
adulthood. Alterations in social behaviors were instead observed only in young
KO animals: during the first 2 weeks of life, KOs emitted longer ultrasonic
vocalizations compared to their WT littermates and as adolescents they displayed
more aggressive behaviors towards a conspecific. These results strongly support
the face validity of the KO2 mouse as a model for FXS, at the same time
demonstrating that its ability to recapitulate social autistic-relevant
phenotypes depends on early testing ages. Autism Res 2017, 10: 1584-1596. © 2017
International Society for Autism Research, Wiley Periodicals, Inc.

© 2017 International Society for Autism Research, Wiley Periodicals, Inc.

DOI: 10.1002/aur.1814
PMID: 28590057 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus