Fmr1 knockout model

Fragile X syndrome

In humans, the absence of the FMR1 protein leads to Fragile X syndrome, which is characterized by a range of symptoms including mental retardation and delays in various neurodevelopmental milestones.

Fmr1 knockout model

The Fmr1 knockout mouse model is perceived as highly translational relevant due to the genetic and phenotypic similarities with patients. It is well known that behavioral phenotypes in this model are lab specific. At Sylics, using our own tests and protocols, we confirmed aberrant social behavior (see image, upper two panels).  Fmrp1 KO mice and wild-type littermates (WT) respond significantly different in the Three Chamber Test of social interaction at 7 weeks of age. WT mice spent more time in the compartment that contained a novel stimulus mouse in comparison with the object compartment during the first 5 min, showing a preference for interaction with a social stimulus rather than an inanimate object. In contrast, Fmrp1 KO did not show a preference for social interaction.

Using Open Field and PhenoTyper cages, we reproduced hyperactivity phenotypes1 that were reported by several other laboratories using this model.

In addition, we found learning deficits in our CognitionWall task (see image, lower two panels). 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).

These phenotypes make the Fmr1 KO mouse a valuable model for mental retardation and autism related drug-screening studies.

1Hyperactivity, 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.