Differential distribution of the MeCP2 splice variants in the postnatal mouse brain.
Mutations in the gene encoding methyl CpG binding protein 2 (MeCP2) are the primary cause of the neurodevelopmental disorder Rett syndrome (RTT). Mecp2-deficient mice develop a neurological phenotype that recapitulates many of the symptoms of RTT, including postnatal onset of the neurological deficits. MeCP2 has two isoforms, MeCP2e1 and MeCP2e2, with distinct amino termini, which are generated by alternative splicing. We examined the distribution of the Mecp2 splice variants in the postnatal mouse brain by in situ hybridization and found regional and age-related differences in transcript abundance. In newborn mice, signals for total Mecp2 and the Mecp2e2 transcripts were widely distributed, with overlapping expression patterns throughout the brain. Expression of the Mecp2e2 splice variant became largely restricted to nuclei within the dorsal thalamus (DT) and cortical layer V in juvenile animals, a pattern that was maintained into adulthood. In contrast, the total Mecp2 riboprobe only weakly labeled the DT and cortical layer V in juvenile and adult animals, although it heavily labeled surrounding brain regions, suggesting that Mecp2e1 is the predominant transcript outside the thalamus. Quantitative real-time PCR was used to measure Mecp2e1 and Mecp2e2 abundance in the diencephalon of adult mice, demonstrating significantly more Mecp2e2 in the DT than in the hypothalamus, which is in agreement with the Mecp2e2 in situ hybridization. The differential distribution of the Mecp2e1 and Mecp2e2 transcripts indicates regional and developmental regulation of Mecp2 splicing in the postnatal mouse brain.
Dragich
Joanna M
JM
Neuroscience Interdepartmental PhD Program, University of California, Los Angeles, Los Angeles, California 90095-1761, USA.
Kim
Yong-Hwan
YH
Arnold
Arthur P
AP
Schanen
N Carolyn
NC
D000367:Age Factors; D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D001931:Brain Mapping; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger