When using mouse models of human diseases, researchers are always haunted by the possibility that the molecular pathologies they tease out may not apply to humans. This dilemma has been partly solved for some heritable human diseases by the creation of disease-specific human embryonic stem (ES) cell lines, as a result of fertility clinics using preimplantation genetic diagnosis to identify embryos carrying disease mutations. The most recent addition to the collection are human ES cells carrying the mutation causing fragile X syndrome, the most common form of hereditary mental retardation.

Embryos diagnosed with serious genetic diseases are never implanted in women undergoing fertility treatment and are discarded. Such embryos have been used to make ES cells carrying mutations for a wide range of 'single-gene' diseases including muscular dystrophy, thalassaemia and Huntington's disease.1

In this month's Cell Stem Cell, Nissim Benvenisty from The Hebrew University, Jerusalem, and Dalit Ben-Yosef from Tel Aviv University report the derivation of an ES cell line from human blastocyst with the mutant gene for fragile X syndrome2.

Previous work had shown that fragile X syndrome occurs because the mutant form of the gene FMR1 is silenced through a cascade of epigenetic modifications, but the mechanism and timing of the changes are not well understood.

Using their new human ES cell line, Benvenisty and colleagues discovered that the undifferentiated stem cells exhibited normal FMR1 expression. Only when the cells differentiated into particular germ layers did the gene stop functioning. The team was also able to dissect out the sequence of regulatory changes that led to the gene silencing2. Now, with a better understanding of the steps involved, the researchers hope that therapeutic techniques can eventually be developed to prevent or reverse FMR1 inactivation in cells with fragile X.