Fragile X Syndrome – Fmr1 KO Mouse Model
Accelerate the availability of targeted FXS therapies with the well-characterized and translationally relevant in vivo Fmr1 KO model
Fragile X Syndrome (FXS) is the most prevalent inherited cause of mild-to-severe cause of intellectual disability and the most common monogenic cause of autism spectrum disorder (ASD). FXS is caused by mutations in the fragile X mental retardation protein 1 (FMR1) gene, resulting in the deficiency of the FMRP protein that plays a key role in synaptogenesis, as well as synaptic plasticity and architecture. The Fmr1 KO mouse model replicates many phenotypic features of human FXS, and therefore, represents a highly translationally relevant mouse model to study efficacy of novel disease-modifying treatments for FXS.
InnoSer is committed to helping industry innovators to accelerate the availability of FXS modifying-treatment to patients through our extensive experience in carrying out efficacy studies in the Fmr1 KO mouse model. Accordingly, InnoSer offers preclinical research services focusing on evaluating therapeutic efficacy in the Fmr1 KO mouse model via multiple validated behavioral readouts.
Take advantage of InnoSer’s expertise, flexibility and collaborative approach for your research. We support our clients in identifying new drugs or applications, characterizing their pharmacological properties, and conducting safety and efficacy testing with state-of-the-art readout capabilities and histopathological analysis.
InnoSer’s neurology expert team possesses relevant experience in working with multiple therapy types ranging from small molecules, peptides, enzymes, oligonucleotides, and gene therapy (viral vectors – e.g.. AAVs).
Fmr1 KO key model characteristics:
- Model is characterized on the C57BL/6J and FVB background.
- Altered spontaneous behaviours, cognitive impairment, hyperactivity, altered anxiety levels, and decreases in social interactions.
- Changes in Event-Related Potentials (ERP) in electrocorticography (ECoG) typically observed in FXS patients are detectable in Fmr1 KO mice.
- Phenotypic similarities observed are confirmed by extensive in-house validation via several protocols using automated home-cage systems (PhenoTyper™) and conventional behavioural tests (portion of results published together with Kramvis et al., 2013).
- Fmr1 KO mice show key FXS characteristics at young age (starting at 6 weeks of age), allowing efficacy testing of targeted interventions as early as post-natal day 1.
Access relevant Fmr1 KO data on C57BL/6J and FVB background here
Key readouts in the Fmr1 KO mouse model
Test the efficacy of your treatments in the following battery of behavioural tests:
Test the efficacy of your treatments with the following biological readouts:
EEG analyses and post-mortem analyses
- Baseline spectral analyses of ECoG data
- Analysis of Auditory event related potentials in ECoG data
- Tissue collection & analysis
Example data featuring the Fmr1 KO mouse model
Fmr1 KO mice show impaired performance in the discrimination learning that can be detected using CognitionWall™ discrimination learning task
Using the CognitionWall™, we developed a one-night automated test to efficiently identify discrimination learning impairments in mice, without time-consuming handling of mice. The CognitionWall™ is a wall with three entrances in front of a food dispenser. Mice are rewarded with a food reward when they choose to pass through one of the three entrances. The rate at which a mouse gains a relative preference for the rewarded entrance is used as a measure of discrimination learning.
Recent literature indicates that clinical EEG recording in FXS patients shows differences in ERP amplitudes; a phenomenon that we also detect in the Fmr1 KO mouse model of FXS.
Experimental setup for auditory event-related potential (AERP) EEG recording. During an ERP recording session, multiple trials are provided with a 100 msec white noise stimulus (~70 dB), with 4-6 sec inter trial interval. Trials with movement artifacts (deducted from XYZ activity) are excluded, generating a clean average AERP trace for the auditory cortex electrode.
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Auditory Event-Related Potentials EEG-Recording
We show similar EEG traces in Fmr1 KO mice, typically observed in FXS patients.
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- Consorthium TD, Bakker CE, Verheij C, Willemsen R, van der Helm R, Oerlemans F, Vermey M, Bygrave A, Hoogeveen A, Oostra BA, Reyniers E. Fmr1 knockout mice: a model to study fragile X mental retardation. Cell. 1994 Jul 15;78(1):23-33.
- Kramvis I, Mansvelder HD, Loos M, Meredith R. Hyperactivity, perseveration and increased responding during attentional rule acquisition in the Fragile X mouse model. Frontiers in behavioral neuroscience. 2013 Nov 21;7:172.