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.
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.
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/
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