title: Experimental autoimmune encephalomyelitis induction in peptidylarginine deiminase 2 knockout mice.
abstract: During the development of multiple sclerosis the destruction of the myelin sheath surrounding the neurites is accompanied by citrullination of several central nervous system (CNS) proteins, including myelin basic protein and glial fibrillary acidic protein. In experimental autoimmune encephalomyelitis (EAE), a disease induced in animals by immunization with proteins or peptides from the CNS, the animals develop symptoms similar to multiple sclerosis (MS). The increased levels of citrullinated CNS proteins associated with MS are also observed during the development of EAE. To study the role of CNS protein citrullination in EAE development, we induced EAE with a peptide derived from myelin oligodendrocyte glycoprotein (MOG(35-55)) in mice lacking the peptidylarginine deiminase 2 (PAD2) protein, because this enzyme was the most likely candidate to be involved in catalyzing CNS protein citrullination in the diseased state. Even though the PAD2 knockout mice displayed a dramatic reduction in the amount of citrullination present in the CNS, indicating that PAD2 is indeed responsible for the majority of detectable citrullination observed in EAE, the development of EAE was not impaired by genetic deletion of PAD2, suggesting that PAD2 catalyzed citrullination is not essential to the development of EAE.
authors.affiliation: Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Reinout
authors.initials: R
authors.lastname: Raijmakers
authors.forename: Judith
authors.initials: J
authors.lastname: Vogelzangs
authors.forename: Jos
authors.initials: J
authors.lastname: Raats
authors.forename: Maret
authors.initials: M
authors.lastname: Panzenbeck
authors.forename: Maureen
authors.initials: M
authors.lastname: Corby
authors.forename: Huiping
authors.initials: H
authors.lastname: Jiang
authors.forename: Michael
authors.initials: M
authors.lastname: Thibodeau
authors.forename: Nancy
authors.initials: N
authors.lastname: Haynes
authors.forename: Walther J
authors.initials: WJ
authors.lastname: van Venrooij
authors.forename: Ger J M
authors.initials: GJ
authors.lastname: Pruijn
authors.forename: Brian
authors.initials: B
authors.lastname: Werneburg
mesh_terms: D000818:Animals; D002956:Citrulline / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology*; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D002956:Citrulline; D006867:Hydrolases; C000620352:PADI2 protein, human; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases