Hypomyelination and cognitive impairment in mice lacking CD133 (Prominin-1)

Abstract

The CD133 antigen, also known as prominin-1, is a glycoprotein that specifically localizes to plasma membrane protrusions. The precise function of CD133 remains unknown, but it is expressed in various progenitor cells including those derived from the neural and hematopoietic system, as well as different tissues. In the adult mouse brain, CD133 is highly expressed in white matter. Here, we performed immunohistochemical staining and electron microscopy to demonstrate that mice lacking CD133 (CD133(-/-)) exhibit decreased myelin in the corpus callosum, the largest white matter tract in the brain. Hypomyelination in CD133(-/-) mice was associated with fewer oligodendrocyte progenitor cells and mature oligodendrocytes. Behavioral analyses revealed that significantly impaired object recognition memory and altered Y-maze performance by CD133(-/-) mice compared with wild-type mice, suggesting perturbed cognitive performance. These results suggest that CD133 regulates myelination and understanding the underlying molecular mechanisms may guide the development of novel therapeutic strategies for diseases characterized by myelin deficiency. (C) 2018 Elsevier Inc. All rights reserved.