Abstract
WW domain-containing oxidoreductase (Wwox) is a putative tumor suppressor. Several germline mutations of Wwox have been associated with infant neurological disorders characterized by epilepsy, growth retardation, and early death. Less is known, however, about the pathological link between Wwox mutations and these disorders or the physiological role of Wwox in brain development. In this study, we examined age-related expression and histological localization of Wwox in forebrains as well as the effects of loss of function mutations in the Wwox gene in the immature cortex of a rat model of lethal dwarfism with epilepsy (lde/lde). Immunostaining revealed that Wwox is expressed in neurons, astrocytes, and oligodendrocytes. lde/lde cortices were characterized by a reduction in neurite growth without a reduced number of neurons, severe reduction in myelination with a reduced number of mature oligodendrocytes, and a reduction in cell populations of astrocytes and microglia. These results indicate that Wwox is essential for normal development of neurons and glial cells in the cerebral cortex.
Highlights
The WW domain-containing oxidoreductase gene (WWOX) is a putative tumor suppressor gene, spanning the second most common chromosomal fragile site (FRA16D) in the human genome
Wwox is considered physiologically indispensable for survival, as Wwox protein is widely expressed throughout the entire body [1,10,11] and the loss of Wwox protein in rodents frequently results in growth retardation and early postnatal death [5,8,12,13]
Western blot analysis showed that Wwox protein was expressed in different parts of the central nervous system (CNS), including the olfactory bulb, cerebral cortex, hippocampus, diencephalon, cerebellum, brain stem, and spinal cord (Figure 1B)
Summary
The WW domain-containing oxidoreductase gene (WWOX) is a putative tumor suppressor gene, spanning the second most common chromosomal fragile site (FRA16D) in the human genome. Wwox protein is highly expressed in the developing nervous system of mouse embryos, with the level of expression and localization of this protein in mouse CNS drastically changing from late embryonicto postnatal-stage [20] These results suggest that Wwox may be important for the development of the CNS and for the maintenance of its normal function. Wwox knockout mice showed neurological disorders with audiogenic epileptic seizures, in addition to severe dwarfism and early postnatal death [25]. These results strongly suggest that Wwox expression is required for the normal development and function of CNS and that mutations in Wwox result in neurological disorders in infants. We analyzed Wwox expression in normal forebrains, as well as pathological changes in the cerebral cortex of lde/lde rats
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
