Experimental autoimmune encephalomyelitis induction in peptidylarginine deiminase 2 knockout mice.
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.
Raijmakers
Reinout
R
Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands.
Vogelzangs
Judith
J
Raats
Jos
J
Panzenbeck
Maret
M
Corby
Maureen
M
Jiang
Huiping
H
Thibodeau
Michael
M
Haynes
Nancy
N
van Venrooij
Walther J
WJ
Pruijn
Ger J M
GJ
Werneburg
Brian
B
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
D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D002956:Citrulline; D006867:Hydrolases; C000620352:PADI2 protein, human; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases