More than 10 distinct lines of Mecp2 mutant mice have been produced. Mice with the deletion of exon 3 (Mecp2tm1.1Jae; Chen et al., 2001), deletion of exons 3 and 4 (Mecp2tm1.1Bird; Guy et al., 2001), and a 308× point mutation (Mecp2tm1Hzo; Shahbazian et al., 2002) are among the best characterized. The complete loss of both MeCP2 protein isoforms were revealed in hemizygous males (Mecp2−/y) of Mecp2tm1.1Jae and Mecp2tm1.1Bird mutants, whereas the 308× mutation in Mecp2tm1Hzo mice introduces a premature stop codon that leads to truncation of the MeCP2 protein (Shahbazian et al., 2002). It should be noted that female heterozygous mice (Mecp2−/+) are the model with best construct validity, as Rett syndrome primarily affects females and is lethal in males in most cases. However, most studies use hemizygous male mice because they develop more severe phenotypes. An important question that remains is why humans are more sensitive than rodents to MeCP2 mutations.
