NEUROLOGICAL DISTURBANCES, PREMATURE LETHALITY, AND CENTRAL MYELINATION DEFICIENCY IN TRANSGENIC MICE OVEREXPRESSING THE HOMEO DOMAIN TRANSCRIPTION FACTOR OCT-6

Pit, Oct, Unc (POU) homeo domain transcription factors hale been impli cated in various developmental processes, including cell division, dif ferentiation, specification, and survival of specific cell types, Alth ough expression of the transcription factor Oct-6 in oligodendroglia i s confined to the promyelin stage and is downregulated at the myelin s tage of development, the effect of Oct-6 overexpression on oligodendro cyte development has not been established, Here we show that transgeni c animals overexpressing Oct-6 at late oligodendrocyte development dev elop a severe neurologic syndrome characterized by action tremors, rec urrent seizures, and premature death. Axons in the central nervous sys tem of Oct-6 transgenics were hypomyelinated, hypermyelinated, or dysm yelinated, and ultrastructural analyses suggested that myelin formatio n was premature, The vulnerability of developing oligodendroglia to Oc t-6 deregulation provides evidence that the POU factor may play a dire ct role in myelin disease pathogenesis in the mammalian CNS.