Altered Dendrites in YFP-MeCP2 Mutant Mice Figure 4. MeCP2J mutant mice have reduced numbers of YFP-expressing cortical neurons. A, C) Fewer YFP+ cells are observed across the entire cortex in mutant males (200 mm coronal sections, , Bregma 22.2 mm in WT). Some cortical regions are more dramatically affected than others, such as visual cortex (red arrow) and auditory cortex (blue arrow). Sharp boundaries correspond to functional regions (Au, auditory; S, somatosensory; V, visual; RS, retrosplenial). Scale bar = 0.5 mm. Overall cortical YFP expression patterns are shown as a qualitative heat map in E), where white indicates few to no neurons and dark orange indicates the most dense cortical labeling. The number of YFP+ cells is generally higher in rostral and medial region in both genotypes. B) Fluorescent Nissl staining (red) of L5 motor cortex. A limited subset of pyramidal neurons express YFP. Scale bar = 100 mm. D) Neuronal density is increased in frontal (Fr), motor (M) and retrosplenial (RS) cortex in mutant mice. F) The percentage of YFP+ pyramidal neurons is reduced in three cortical regions (F, frontal; M, motor; RS, retrosplenial). doi:10.1371/journal.pone.0031896.g004 populations. In MeCP2J mice, our secondary apical dendrite spine density values are in close agreement with those previously reported for Golgi-stained L5 motor cortical neurons [34]. By contrast, in a comparable study that used a highly similar transgenic cell population (Thy-1-GFP-labeled L5 neurons in the motor cortex), but harboring the protein-null MeCP2B mutation, spine density was significantly reduced in all dendritic compart- ments analyzed, including primary apical, secondary apical, and basal dendrites [32]. In L2/3 pyramidal neurons, MeCP2J mutant cells were reported to exhibit no changes in spine density, but had relatively large reductions in both apical and basal dendritic branching [28,29,31]. At the other phenotypic extreme, in the B6.129S-Mecp2tm1Hzo/J (MeCP2308/Y) mouse line, which has a C- terminal truncating deletion in MeCP2, neither dendritic branching nor spine density are affected, in both L2/3 as well as L5 cells [26]. PLoS ONE | www.plosone.org 6 March 2012 | Volume 7 | Issue 3 | e31896