Are dopamine receptor and transporter changes in Rett syndrome reflected in Mecp2-deficient mice?

We tested the claim that the dopaminergic dysfunction of Rett Syndrome (RTT) also occurs in Mecp2-deficient mice that serve as a model of the syndrome. We used positron emission tomography (PET) to image dopamine D2 receptors (D2 R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D1 R and D2 R density was measured in postmortem human tissue by autoradiography. Results showed 1) significantly reduced D2 R density in the striatum of women with RTT compared to control subjects. 2) PET imaging of mouse striatum similarly demonstrated significant reductions in D2 R density of 7-10 week-old hemizygous (Mecp2-null) and heterozygous (HET) mice compared to wild type (WT) mice. With age, the density of D2 R declined in WT mice but not HET mice. 3) In contrast, postmortem autoradiography revealed no group differences in the density of D1 R and D2 R in the caudate and putamen of RTT versus normal control subjects. 4) In humans and in the mouse model, PET revealed only marginal group differences in DAT. The results confirm that dopaminergic dysfunction in RTT is also present in Mecp2-deficient mice and that reductions in D2 R more likely explain the impaired ambulation and progressive rigidity observed rather than alterations in DAT.