Although the fragile X gene (FMR1) was isolated more than four years ago, little is known about its physiologic function and the pathological mechanisms that lead to the abnormalities observed in fragile X patients. To provide more insight into the physiologic role of FMR1, we have developed a transgenic mouse with a loss‐of‐function (Knockout) mutation in the FMR1 gene using homologous recombination in embryonic stem cells. The mutant mice lack normal FMR1 mRNA and protein, as is also the case in human fragile X syndrome. The mice show enlarged testes and impaired performance in cognitive function tests, a clinical picture very similar to that of human patients. As a consequence, this animal model might be useful in elucidating the physiologic function of FMR1 and the pathological mechanisms that lead to mental retardation and behavioral abnormalities in fragile X syndrome. Experimental drug treatment can now be tried to ameliorate the congnitive function and behavior of affected mice and, if these experiments are successful, human trials can be initiated. Furthermore, gene therapy experiments by introduction of a foreign FMR1 gene into mutant mice can now be begun.

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doi.org/10.1002/mrdd.1410010412, hdl.handle.net/1765/93577
Developmental Disabilities Research Reviews
Department of Clinical Genetics

Willems, P., Reyniers, E., & Oostra, B. (1995). An animal model for fragilex syndrome. Developmental Disabilities Research Reviews, 1(4), 298–302. doi:10.1002/mrdd.1410010412