Respiratory Dysfunction in a Mouse Model of Rett Syndrome, an Autism Spectrum Disorder

Rett syndrome (RTT) is a neurodevelopmental disorder caused almost exclusively by mutations in the MECP2 gene. Because respiratory abnormalities (apneas or temporary pauses in breathing) are a prominent feature of this disorder, the present study investigated whether or not Mecp2^{tm1.1Jae heterozygous} (Het) female mice, a model of RTT, also exhibit breathing abnormalities. Nine wild-type (WT) mice were compared with eight Mecp2 Het mice. Following intraperitoneal injections of 0.9% NaCl (10 uL/g) (as a subset of a drug-response trial, this experiment required saline injections in order to minimize variable factors), the mice were placed in whole body plethysmography chambers (EMMS) to measure breathing, and behavior was monitored by video recording. The same procedure was repeated after one week. Apneas/minute and apnea length were determined by observing each subject’s breathing activity. Any pause in breathing greater than twice the average expiration time (Te) was defined as an apnea. The paired t-test was used to compare mean values of apneas/minute and apnea length in the WT versus Het mice. Fourteen observations were recorded in each group. Mean apneas/minute was 0.66 ± 0.06 in the WT mice and 1.47 ± 0.24 in the Het mice. The difference was statistically significant, t = 3.23 (p = 0.003). Mean apnea length was 1.19 ± 0.45 seconds in WT-mice and 2.01 ± 2.61 in Het-mice with no significant difference, t = 1.15 (p = 0.25). Therefore, there was significant increase in apneas/minute in the Mecp2 Het mice compared to WT subjects, indicating that apneas/minute can be used as a reliable parameter to assess the therapeutic response to various experimental therapies in the RTT mouse model.