Wild-type MeCp2 expression coincides with age-dependent sensory phenotypes in a female mouse model for Rett syndrome

J Neurosci Res. 2023 Apr 7. doi: 10.1002/jnr.25190. Online ahead of print.ABSTRACTRett syndrome is characterized by an early period of typical development and then, regression of learned motor and speech skills in girls. Loss of MECP2 protein is thought to cause Rett syndrome phenotypes. The specific underlying mechanisms from typical developmental trajectory to regression features throughout life are unclear. Lack of established timelines to study the molecular, cellular, and behavioral features of regression in female mouse models is a major contributing factor. Due to random X-chromosome inactivation, female patients with Rett syndrome and female mouse models for Rett syndrome (Mecp2Heterozygous , Het) express a functional copy of wild-type MeCp-2 protein in approximately half of all cells. As MeCp2 expression is regulated during early postnatal development and experience, we characterized the expression of wild-type MeCp2 in the primary somatosensory cortex of female Het mice. Here, we report increased MeCp2 levels in non-parvalbumin-positive neurons of 6-week-old adolescent Het relative to age-matched wild-type controls, while also displaying typical levels of perineuronal net expression in the barrel field subregion of the primary somatosensory cortex, mild tactile sensory perception deficits, and efficient pup retrieval behavior. In contrast, 12-week-old adult Het express MeCp2 at levels similar to age-matched wild-type mice, show increased perineuronal net expression ...
Source: Cell Research - Category: Cytology Authors: Source Type: research