The Journal of Neuroscience, October 29, 2003, 23(30):9817-9823
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Cellular/Molecular
Discrete Gene Loci Regulate Neurodegeneration, Lymphocyte Infiltration, and Major Histocompatibility Complex Class II Expression in the CNS
Olle Lidman,1
Maria Swanberg,1
Linn Horvath,2
Karl W. Broman,3
Tomas Olsson,1 * and
Fredrik Piehl1 *
Departments of 1Clinical Neuroscience, Neuroimmunology Unit and 2Medicine, Rheumatology Research Unit, Karolinska Institute, Karolinska Hospital, S-17176, Stockholm, Sweden, and 3Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland 21205
Neurodegeneration and inflammation are fundamental aspects of many neurological diseases. A genome-wide scan of the response to ventral root avulsion (VRA) in a rat F2 cross discloses specific gene regions that regulate these processes. Two gene loci displayed linkage to neurodegeneration and T cell infiltration, respectively, and a single locus displayed extreme linkage to VRA-induced major histocompatibility complex class II expression on microglia. The demonstration that polymorphic genes in different loci control neurodegeneration and CNS inflammation has implications for various experimental rodent nervous system paradigms and potentially for genetically regulated susceptibility to a variety of human CNS diseases.
Key words: axotomy; motoneuron; degeneration; immunity; microglia; mapping
Received July 21, 2003;
revised September 2, 2003;
accepted September 3, 2003.
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K. Harnesk, M. Swanberg, J. Ockinger, M. Diez, O. Lidman, E. Wallstrom, A. Lobell, T. Olsson, and F. Piehl
Vra4 Congenic Rats with Allelic Differences in the Class II Transactivator Gene Display Altered Susceptibility to Experimental Autoimmune Encephalomyelitis
J. Immunol.,
March 1, 2008;
180(5):
3289 - 3296.
[Abstract]
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