Rett syndrome (RTT) is an X-linked neurodevelopmental disorder due to mutations 
affecting the neural transcription factor MeCP2. Approximately 50% of affected 
females have decreased bone mass. We studied osteoblast function using a murine 
model of RTT. Female heterozygote (HET) and male Mecp2-null mice were compared 
to wild type (WT) mice. Micro-CT of tibia from 5 week-old Mecp2-null mice showed 
significant alterations in trabecular bone including reductions in bone volume 
fraction (-29%), number (-19%), thickness (-9%) and connectivity density (-32%), 
and increases in trabecular separation (+28%) compared to WT. We also found 
significant reductions in cortical bone thickness (-18%) and in polar moment of 
inertia (-45%). In contrast, cortical and trabecular bone from 8 week-old WT and 
HET female mice were not significantly different. However, mineral apposition 
rate, mineralizing surface and bone formation rate/bone surface were each 
decreased in HET and Mecp2-null mice compared to WT mice. Histomorphometric 
analysis of femurs showed decreased numbers of osteoblasts but similar numbers 
of osteoclasts compared to WT, altered osteoblast morphology and decreased 
tissue synthesis of alkaline phosphatase in Mecp2-null and HET mice. Osteoblasts 
cultured from Mecp2-null mice, which unlike WT osteoblasts did not express 
MeCP2, had increased growth rates, but reductions in mRNA expression of type I 
collagen, Runx2 and Osterix compared to WT osteoblasts. These results indicate 
that MeCP2 deficiency leads to altered bone growth. Osteoblast dysfunction was 
more marked in Mecp2-null male than in HET female mice, suggesting that 
expression of MeCP2 plays a critical role in bone development.