Introduction of aFMR1 transgene in the fragile X knockout mouse

Patients with fragile X syndrome show mental retardation, behavioural abnormalities, facial anomalies and macroorchidism due to the lack of the FMR1 protein (FMRP). Recently a knockout mouse model for fragile X syndrome has been made through homologous recombination of the murine Fmr1 gene by an inactivated Fmr1 gene construct in embryonic stem cells. The knockout mouse lacks Fmrp and shows symptoms similar to those found in fragile X patients. To answer the question whether reintroduction of Fmrp can restore the normal phenotype a transgenic mouse was generated expressing human FMRP, The FMR1 transgene was under control of a CMV promoter to obtain ubiquitous FMRP expression. Transgenic mice were crossed with knockout mice to obtain a transgenic knockout mouse. The rescue mouse did express FMR1 protein, but did not show a reversal of the phenotype, most likely because the level of FMRP expressed from the transgene is inadequate or not time or cell specific.