The Syndrome of X-linked mental retardation with fragile X is the single most common form of inherited mental retardation. The fragile X Syndrome is the result of amplification of a simple repeated DNA sequence CGG located within the first exon of FMR-1, a gene encoding an RNA-binding protein./ In normal individuals, the first exon of FMR-1 contains between 2 and 60 copies, in tandem, of CGG, with an occasional TGG, thought to stabilize the repeat, occurring once every 7-25 CGG repeat units. In some individuals, the number of trinucleotide repeats is increased to between 60 and 200, making them carriers of a clinically silent """"""""premutation"""""""", which, however, can expand in their offspring to a full mutation containing hundreds to thousands of copies of the repeat and leading to loss of FMR1 expression. A stretch of the CGG repeats cloned originally from a Fragile X affected male and containing 86 copies, with two TGG interruptions, was injected into mice. The transgenic mice show no alteration in the size of the repeat upon passage through the murine germline, regardless of the sex of transmitting parent. Another construct, made entirely in vitro without cloning, has 32, 80 and 128 repeats that contain 9,57, and 105 uninterrupted CGG repeats located at the 3' end of the repeated DNA in a minigene containing the FMR-1 promoter and a downstream reporter gene. This construct was also injected into fertilized murine oocytes to establish transgenic lines. This construct also appears to be stable during initial passages through the murine germline.
