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

Gaudissard, Julie; Ginger, Melanie; Premoli, Marika; Memo, Maurizio; Frick, Andreas; Pietropaolo, Susanna

doi:10.1002/aur.1814

Cited by 44 publications

(74 citation statements)

References 55 publications

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“…Importantly, physical activity behavior is mostly centrally regulated and thus could be a possible consequence of Fmr1- deficiency in the CNS. Increased daily locomotor activity alterations had been previously well-documented in Drosophila FXS model (34) and in younger 8 weeks-old male Fmr1 -KO animals (35). Our results indicate that 4-months old Fmr1 -deficient mice display a sustained increase in physical activity as compared to wildtype mice, suggesting that hyperactivity-related phenotypes are not transient and persist in adulthood.…”

Section: Discussionmentioning

confidence: 79%

Fmr1-Deficiency Impacts Body Composition, Skeleton, and Bone Microstructure in a Mouse Model of Fragile X Syndrome

et al. 2019

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Fragile X syndrome (FXS) is a neurodevelopmental disorder associated with intellectual disability, hyperactivity, and autism. FXS is due to the silencing of the X-linked FMR1 gene. Murine models of FXS, knock-out (KO) for the murine homolog Fmr1, have been generated, exhibiting CNS-related behavioral, and neuronal anomalies reminiscent of the human phenotypes. As a reflection of the almost ubiquitous expression of the FMR1 gene, FXS is also accompanied by physical abnormalities. This suggests that the FMR1-deficiency could impact skeletal ontogenesis. In the present study, we highlight that Fmr1-KO mice display changes in body composition with an increase in body weight, likely due to both increase of skeleton length and muscular mass along with reduced visceral adiposity. We also show that, while Fmr1-deficiency has no overt impact on cortical bone mineral density (BMD), cortical thickness was increased, and cortical eccentricity was decreased in the femurs from Fmr1-KO mice as compared to controls. Also, trabecular pore volume was reduced and trabecular thickness distribution was shifted toward higher ranges in Fmr1-KO femurs. Finally, we show that Fmr1-KO mice display increased physical activity. Although the precise molecular signaling mechanism that produces these skeletal and bone microstructure changes remains to be determined, our study warrants further investigation on the impact of FMR1-deficiency on whole-body composition, as well as skeletal and bone architecture.

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Section: Discussionmentioning

confidence: 79%

Fmr1-Deficiency Impacts Body Composition, Skeleton, and Bone Microstructure in a Mouse Model of Fragile X Syndrome

et al. 2019

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“…The majority of studies (>260) has been performed with the first mouse model, the Fmr1 KO mouse (Bakker et al, 1994 ), which is characterized by a complete loss of FMRP and expression of abnormal mRNA (Yan et al, 2004 ; Mientjes et al, 2006 ). To investigate a potential effect of the aberrant mRNA, another model, the Fmr1 KO2 mouse was generated in 2006 (Mientjes et al, 2006 ), which does not express any mRNA, but no significant differences between the two animal models were found (Gaudissard et al, 2017 ). By now, the KO2 animals have been employed in more than 20 studies.…”

Section: The Fragile X Syndrome — Of Micementioning

confidence: 99%

Of Men and Mice: Modeling the Fragile X Syndrome

Dahlhaus

2018

Front. Mol. Neurosci.

112

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The Fragile X Syndrome (FXS) is one of the most common forms of inherited intellectual disability in all human societies. Caused by the transcriptional silencing of a single gene, the fragile x mental retardation gene FMR1, FXS is characterized by a variety of symptoms, which range from mental disabilities to autism and epilepsy. More than 20 years ago, a first animal model was described, the Fmr1 knock-out mouse. Several other models have been developed since then, including conditional knock-out mice, knock-out rats, a zebrafish and a drosophila model. Using these model systems, various targets for potential pharmaceutical treatments have been identified and many treatments have been shown to be efficient in preclinical studies. However, all attempts to turn these findings into a therapy for patients have failed thus far. In this review, I will discuss underlying difficulties and address potential alternatives for our future research.

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“…Mice ultrasonic communication analysis has become an important tool for behavioural readout and monitoring 12,13 . Altered calling patterns are detected in different mouse models of NDDs, especially in models of autism spectrum disorders (ASD); for example, BTBR T + tf/J 14,15 and Fmr1-KO (knock-out) mice 16–19 showed quantitative and qualitative alterations from their wild-type controls (WT) during infancy and in adulthood. Ultrasonic communication deficits were also found in other mouse models of ASD, such as the Shank mouse lines 20–22 and Ctnap2 KO mice 23 .…”

Section: Introductionmentioning

confidence: 99%

Specific profile of ultrasonic communication in a mouse model of neurodevelopmental disorders

Premoli

Bonini

Mastinu

et al. 2019

Sci Rep

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Mice emit ultrasonic vocalizations (USVs) in different social conditions: pups maternal separation, juveniles play, adults mating and social investigation. The USVs measurement has become an important instrument for behavioural phenotyping in neurodevelopmental disorders (NDDs). Recently, we have demonstrated that the deletion of the NFκB1 gene, which encodes the p50 NF-κB subunit, causes NDDs phenotype in mice. In this study, we investigated the ultrasonic communication and the effects of an early social enrichment in mice lacking the NF-κB p50 subunit (p50 KO). In particular, USVs of wild-type (WT), p50 KO and KO exposed to early social enrichment (KO enriched) were recorded using an ultrasound sensitive microphone and analysed by Avisoft software. USVs analysis showed that p50 KO pups emit more and longer vocalizations compared to WT pups. On the contrary, in adulthood, p50 KO mice emit less USVs than WT mice. We also found significant qualitative differences in p50 KO mice USVs compared to WT mice; the changes specifically involved two USVs categories. Early social enrichment had no effect on USVs number, duration and type in p50 KO mice. Together, these data revealed social communication alterations in a mouse model of NDDs; these deficits were not recovered by early social enrichment, strengthening the fact that genetic background prevails on environmental enrichment.

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

Cited by 44 publications

References 55 publications

Fmr1-Deficiency Impacts Body Composition, Skeleton, and Bone Microstructure in a Mouse Model of Fragile X Syndrome

Fmr1-Deficiency Impacts Body Composition, Skeleton, and Bone Microstructure in a Mouse Model of Fragile X Syndrome

Of Men and Mice: Modeling the Fragile X Syndrome

Specific profile of ultrasonic communication in a mouse model of neurodevelopmental disorders

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