LONG-TERM FOLLOW-UP OF MECP2-KNOCKOUT MICE USING MAGNETIC RESONANCE TECHNIQUES

Objectives: Rett syndrome is not a rare neurodevelopmental disorder, characterized by microcephaly, seizures, psychomotor retardation, and stereotype movements. The prevalence rate of Rett syndrome is around 1:10,000 to 1:23,000 live female births. Eighty percent of patients with Rett syndrome are found to have MeCP2 mutation. However, the long-term effect of MeCP2 mutation on neurons remains controversial.

Methods: To investigate the long-term effect of MeCP2 mutation on neurons, MeCP2-knockout mice and control mice were evaluated in the present study using MR techniques. The MR techniques used included diffusion tensor imaging (DTI), T2-weighted imaging, and proton magnetic resonance spectroscopy (MRS). The body weight change and brain volume were recorded.

Results: We found that the MeCP2-knockout mice began to develop neurological symptoms at 5–6 weeks old, characterized by the change in hindlimb movements. Compared with control mice, there was a significant loss of brain volume for MeCP2-knockout mice. During the follow-up period, there was a significant decrease of choline signal in striatum of MeCP2 mice in MRS. In DTI measurements, the change in landa1 was significantly larger than that for the average of landa 2+3, indicating that the early effect of MeCP2 mutation mainly affect neurons rather than myelin integrity.

Conclusion: Our preliminary results confirm the previous findings that MeCP2 mutation mainly affects the neurons. However, the minor change in myelin integrity and the decrease in choline indicated that glial cells may also be involved in MeCP2-knockout mice.