Fragile X syndrome

Fragile X syndrome is caused by lack of expression of the FMR1 gene

In patients, lack of expression of the FMR1 gene and absence of the FMRP protein leads to Fragile X syndrome. This syndrome is characterized by a range of symptoms including mental retardation, delays in neurodevelopmental milestones, and autistic behavior. Some existing therapies help to reduce symptoms, but there is no disease modifying treatment for Fragile X syndrome.

Fmr1 knockout (KO) model

Genetic mutations were engineered in mice to mimic the loss of expression of the FMR1 gene in patients. Fmr1 knockout mice are perceived as translationally relevant due to the genetic and phenotypic similarities with patients. At Sylics, we use the Fmr1 knockout mutant that was created by an academic group in Rotterdam, The Netherlands (Bakker et al. 1994). At Sylics, using our own tests and protocols, we have confirmed a number of these phenotypes.

In the three chamber test for social interaction, WT mice spent more time in the compartment that contained a novel stimulus mouse in comparison with the object compartment. In contrast to WT mice, Fmrp1 KO did not show a preference for social interaction.

Aberrant activity response in Fmr1 KO mice

Using Open Field and PhenoTyper cages, we reproduced hyperactivity phenotypes that were reported by several other laboratories using this model. In addition we published that Fragile X mice show hyperactivity, perseveration and increased responding during attentional rule acquisition in an operant test (Kramvis et al., 2013).

Aberrant cognitive performance in Fmr1 KO mice

Early reports showed deficits in Fmr1 KO mice in cognitive tests such as the morris water maze. At Sylics, we detected impaired performance of Fmr1 KO mice in the Discrimination Learning phase of the CognitionWall task compared to wild-type litter mates. Fmr1 KO mice require more entries to reach a performance of 90% correct entries in comparison with WT littermates, both a 6 weeks of age as shown and at 12 weeks of age.

Fmr1 KO mice require more entries to reach a performance of 90% correct entries in comparison with WT littermates, both a 6 weeks of age as shown and at 12 weeks of age (not shown).

Aberrant social behavior in Fmr1 KO mice

Social behavior in mice can be tested in the Three Chamber Test of social interaction. Normal wild-type mice have a preference for interacting with another mouse rather than an inanimate object. In contrast, Fmrp1 KO did not show a preference for social interaction over interaction with an inanimate object.

Kramvis et al. (2013) Front Behav Neurosci

Hyperactivity, perseveration and increased responding during attentional rule acquisition in the Fragile X mouse model. Kramvis I, Mansvelder HD, Loos M, Meredith R. Front Behav Neurosci. 2013 Nov 21;7:172. doi: 10.3389/fnbeh.2013.00172. PMID: 24312033; PMCID: PMC3836024. https://pubmed.ncbi.nlm.nih.gov/24312033/

More information

Please reach out to us if you want to learn more about our FMR1 Fragile X solutions. We will contact you within 1 business day.

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.