Loss of Testicular Orphan Receptor 4 Impairs Normal Myelination in Mouse Forebrain

Testicular orphan nuclear receptor 4 (TR4) has been suggested to play important roles in the development and functioning of the central nervous system (CNS). We find reduced myelination in TR4 knockout (TR4−/−) mice, which is particularly obvious in forebrains and in early developmental stages. Further analysis reveals that CC-1-positive (CC-1+) oligodendrocytes are decreased in TR4−/− forebrains. The O4+ signals are also reduced in TR4−/− forebrains when examined at postnatal d 7. However, the number and proliferation rate of platelet-derived growth factor receptor α-positive (PDGFαR+) oligodendrocyte precursor cells (OPCs) remain unaffected in these regions, suggesting that loss of TR4 interrupts oligodendrocyte differentiation. This is further supported by the observation that CC-1+ oligodendrocytes derived from 5-bromo-2′-deoxyuridine incorporating OPCs are significantly reduced in TR4−/− forebrains. We also find higher Jagged1 expression levels in axon fiber-enriched regions in TR4−/− forebrains, sug...