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Spp1 Appears to Be a Key Gene for Sporadic Obstructive Hydrocephalus in the Absence of AQP4
Miriam Echevarría1,2, Laura Hiraldo-González1,2, José Luis Trillo-Contreras1,2
1Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain.
Abstract:
Aquaporin-4 (AQP4) is expressed in ependymal cells bordering the ventricles, the glia limitans, and pericapillary astrocyte endfeet forming the blood-brain barrier. The sporadic occurrence of obstructive congenital hydrocephalus (OH) has been observed in the offspring of AQP4-/- mice generated in the CD1 strain background. Here, we used microarray analysis to explore gene expression profiles in the periaqueductal area from littermate AQP4-/- pups at postnatal day 12. We compared wild-type (WT) animals with AQP4-/- animals that developed OH (AQP4-/--OH) and those that did not (AQP4-/--NH). Bioinformatic analysis identified gene sets associated with proliferation and migration of microglia, ependymal cell adhesion, extracellular matrix components, axon myelination, and neuronal synapsis. Among the differentially expressed genes, Spp1-expressed by neonatal CD11c+ microglia-was highlighted in the triple comparison. Spp1 was significantly upregulated in AQP4-/--NH and downregulated in AQP4-/--OH mice. These findings suggest that CD11c+ microglia, via Spp1 expression, play a key morphogenic role in the aqueduct of Sylvius and their absence, occurring in a small subset of AQP4-/--CD1 animals, leads to obstructive hydrocephalus.
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