The postnatal expression of transcripts and proteins in the corpus callosum, as well as its myelinization, is affected by the congenital absence of AQP4.

During postnatal development in mice there is a marked switch in the expression of AQP4 from white to grey matter regions. A microglial population, CD11c+, which has been shown to be involved in normal postnatal development of the corpus callosum (CC), prolongs its expression in this tissue in the absence of AQP4. Here, we investigated the correlation between the levels of AQP4 expression during the early postnatal period and the expression of marker genes related to oligodendrogenesis in the mouse CC. A microarray transcriptomic analysis of the CC of wild-type (WT) and AQP4-KO (KO) mice was performed, validation of differentially expressed genes was done by RT-qPCR, and protein expression was analyzed by immunofluorescence. Overexpression of genes associated with microglia and astrocytes and inhibition of genes associated with mature oligodendrocytes were observed in the KO animal compared to the WT. GFAP and CD11c signals were significantly higher in the CC of the KO animal, as was the number of OPCs (OLIG2+/PDGFRa+). However, the number of mature oligodendrocytes (OLIG2+/CC1+) was reduced in the KO mice, indicating a failure of the oligodendrogenesis process that results in a significant reduction in the number of myelinated axons in the CC of the KO animal. This mouse model of congenital AQP4 deficiency, which shows defects in the maturation of its oligodendrocytes in the CC, provides insight into the role of AQP4 in demyelinating pathology and could help in the development of new diagnostic and/or therapeutic strategies for such diseases.