Dr. Bird and colleagues made the discovery using genetically engineered mice, whose MECP2 gene was silenced by a so-called stop cassette. The silencing could be reversed at will by administering the estrogen analog tamoxifen(Drug information on tamoxifen).
The researchers measured symptoms in the mice with observational tests for such things as gait, tremor, irregular breathing, and poor ability to clasp with the hind limbs. A wild-type mouse would score zero for all symptoms, while mice with the syndrome would score one if a symptom was present and two if it was severe.
The key experiment, Dr. Bird and colleagues said, was in female mice that had developed symptoms:
- Wild-type littermates had no symptoms, as expected.
- Untreated experimental animals had symptom scores averaging above four.
- Mice treated with tamoxifen over a four-week period (thus slowly reactivating their MECP2 gene) saw their symptom scores progressively reduced, to one or below.
- The difference in symptom scores between the two groups of experimental mice was significant at P<0.002.