Models Of

A successful unstable triplet repeat has never been made in a mouse model as mouse genes do not have the same susceptibility to this particular repeat expansion as human genes do. However it is possible to delete the FMR1 gene in mice. The FMR1 gene is highly conserved in the mouse, with an amino acid and nucleotide sequences of 95% and 97%, respectively15. The mouse model has subtle behavioral symptoms that resemble some of those in the human disease, including mild spatial learning deficits16-18. The startle response in these animals has been reported to be both increased and decreased; however the background strain of the mouse can complicate the expression of subtle phenotypes19. One of the more robust phenotypes of the mice is macro-orchidism, with an increase in testicular size by about 30% in 6-month-old knockouts when compared to wild-type controls20,21. Macro-orchidism, seen in human patients, is caused from an increase increase in Sertoli cell proliferation 22 . Like their human counterparts, mice with FXS are more prone to seizures and exhibit subtle gross anatomical brain abnormalities23.

A homologous gene to FMR1, dFMR1 has been found in Drosophila24, and flies deficient in this gene exhibit phenotypic characteristics that include deficiencies in learning courtship behavior, and abnormal neurite extension, guidance, and branching25,26.

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