title: De-repression of myelin-regulating gene expression after status epilepticus in mice lacking the C/EBP homologous protein CHOP.
abstract: The C/EBP homologous protein CHOP is normally present at low levels in cells but increases rapidly after insults such as DNA damage or endoplasmatic reticulum stress where it contributes to cellular homeostasis and apoptosis. By forming heterodimers with other transcription factors, CHOP can either act as a dominant-negative regulator of gene expression or to induce the expression of target genes. Recent work demonstrated that seizure-induced hippocampal damage is significantly worse in mice lacking CHOP and these animals go on to develop an aggravated epileptic phenotype. To identify novel CHOP-controlled target genes which potentially influence the epileptic phenotype, we performed a bioinformatics analysis of tissue microarrays from chop-deficient mice after prolonged seizures. GO analysis revealed genes associated with biological membranes were prominent among those in the chop-deficient array dataset and we identified myelin-associated genes to be particularly de-repressed. These data suggest CHOP might act as an inhibitor of myelin-associated processes in the brain and could be targeted to influence axonal regeneration or reorganisation.
authors.affiliation: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland Dublin, Ireland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sheedy
authors.affiliation: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland Dublin, Ireland.
authors.forename: Claire
authors.initials: C
authors.lastname: Mooney
authors.affiliation: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland Dublin, Ireland.
authors.forename: Eva
authors.initials: E
authors.lastname: Jimenez-Mateos
authors.affiliation: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland Dublin, Ireland.
authors.forename: Amaya
authors.initials: A
authors.lastname: Sanz-Rodriguez
authors.affiliation: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland Dublin, Ireland.
authors.forename: Elena
authors.initials: E
authors.lastname: Langa
authors.affiliation: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland Dublin, Ireland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Mooney
authors.affiliation: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland Dublin, Ireland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Engel
keywords: CHOP; epilepsy; mRNA microarray; myelin basic protein; status epilepticus