Table 1.

Phosphorylation-defective Mecp2 mouse models.

	Animal phenotype	Synaptic physiology	Molecular Phenotype	Importance
Mecp2S80A; Tao et al., 2009	Normal lifespan;		Decreased binding to chromatin on specific gene promoters.	S80 phosphorylation regulates MeCP2 function in resting neurons.
	RTT-like phenotype;
	−62% locomotor activity in dark cycle running wheel assays.
Mecp2T308A; Ebert et al., 2013	Normal body weight;		T308A mutation does not alter MeCP2 stability, binding to DNA and basal interaction with NCoR complex;	Loss of phosphorylation-dependent interaction of MeCP2 with NCoR contributes to the development of some neurological defects observed in RTT.
	Reduced brain weight;
	More seizures and lower seizure threshold;
	Locomotor defects.		Decrease in membrane depolarization-induced Npas4 and Bdnf expression.
Mecp2S421A; Cohen et al., 2011	No visible differences compared to their wild type littermates;	Increased dendritic complexity;	No detectable effect on gene transcription.	S421 phosphorylation has a role in synaptic connections development within the cerebral cortex.
	No locomotor defects;	Increased mIPSC amplitude.
	Behavioral abnormalities outlined with sociability and preference for social novelty assays.
Mecp2S421A;S424A; Tao et al., 2009; Li et al., 2011	Normal lifespan;	Stronger LTP induced at both the Schaffer collateral-CA1 synapse and the mossy fiber-CA3 synapse, compared to wild type;	Hippocampal Mecp2S421A;S424A neurons show an increase in Bmp4 and Bdnf transcription and a decrease in Mef2c and Grm1 transcription.	S421 phosphorylation is a neuronal-activity induced event.
	No RTT-like phenotype;
	+145% locomotor activity in dark cycle running wheel assays;
	Fear-conditioning test and Morris water maze test suggest an altered hippocampus function.	Increased excitatory synaptogenesis in both the hippocampal and cortical neurons.