Eae19, a new locus on rat chromosome 15 regulating experimental autoimmune encephalomyelitis.
Multiple sclerosis (MS) and its animal model, myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE), share a complex genetic predisposition with contributions from the major histocompatibility complex class II genes and many other genes. Linkage mapping in F(2) crosses between the susceptible DA rat strain and the resistant ACI or BN rat strains in various models of autoimmune neuroinflammation have repeatedly displayed suggestive linkage to a region on rat chromosome 15. A direct study of this region was undertaken in congenic strains by transferring resistant ACI alleles to the susceptible DA background. Phenotypic analysis demonstrated lower maximal and cumulative EAE scores in the DA.ACI-D15Rat6-D15Rat71 (C15), DA.ACI-D15Rat6-D15Rat48, D15Rat126-D15Rat71 (C15R3b), and DA.ACI-D15Rat23-D15rat71 (C15R4) strains compared to the parental DA rat strain. Linkage analysis was then performed in a (DA x PVG.AV1)F(7) advanced intercross line, resulting in a LOD score of 4.7 for the maximal EAE score phenotype at the peak marker D15Rat71 and a confidence interval of 13 Mb, overlapping with the congenic fragment defined by the C15R3b and the C15R4 strains. Thus, a new MOG-EAE locus with the designation Eae19 is identified on rat chromosome 15. There are 32 confirmed or predicted genes in the confidence interval, including immune-responsive gene 1 and neuronal ceroid lipofuscinose gene 5. Definition of loci such as Eae19 enables the characterization of genetically regulated, evolutionary conserved disease pathways in complex neuroinflammatory diseases.
Sheng
Jian Rong
JR
Center for Molecular Medicine, Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.
Jagodic
Maja
M
Dahlman
Ingrid
I
Becanovic
Kristina
K
Nohra
Rita
R
Marta
Monica
M
Iacobaeus
Ellen
E
Olsson
Tomas
T
Wallström
Erik
E
D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D008040:Genetic Linkage; D016013:Likelihood Functions; D008126:Lod Score; D051381:Rats; D013997:Time Factors
Hum Mol Genet. 1999 Nov;8(12):2183-90
10545597
J Immunol. 1995 May 15;154(10):5536-41
7537310
Cancer Res. 2000 Feb 15;60(4):1092-6
10706129
Genome Res. 2000 Apr;10(4):473-82
10779487
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6670-5
10841565
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1787-92
11172029
Trends Mol Med. 2001 Mar;7(3):115-21
11286782
Genes Immun. 2001 Jun;2(4):205-10
11477475
Immunogenetics. 2001 Jul;53(5):410-5
11486278
Nat Genet. 1995 Jul;10(3):313-7
7545492
Nature. 1995 Sep 14;377(6545):150-1
7675080
Nat Genet. 1995 Nov;11(3):241-7
7581446
J Neuroimmunol. 1995 Dec;63(1):17-27
8557821
Genetics. 1995 Nov;141(3):1199-207
8582624
Lancet. 1996 Jun 22;347(9017):1728-30
8656905
Nat Genet. 1996 Aug;13(4):464-8
8696343
Nat Genet. 1996 Aug;13(4):469-71
8696344
Nat Genet. 1996 Aug;13(4):472-6
8696345
Curr Opin Neurol. 1996 Jun;9(3):155-8
8839605
Brain Pathol. 1996 Jul;6(3):259-74
8864283
Genetics. 1997 Apr;145(4):1201-18
9093869
Behav Genet. 1997 Mar;27(2):125-32
9145551
Immunol Today. 1997 Oct;18(10):472-7
9357138
Am J Hum Genet. 1997 Dec;61(6):1379-87
9399895
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9979-84
9707586
J Clin Invest. 1998 Sep 15;102(6):1265-73
9739061
J Immunol. 1998 Oct 15;161(8):4411-9
9780220
Brain. 1998 Oct;121 ( Pt 10):1869-87
9798743
Eur J Immunol. 1998 Oct;28(10):3329-35
9808202
J Immunol. 1999 Mar 1;162(5):2581-8
10072499
Eur J Hum Genet. 2001 Aug;9(8):621-6
11528508
J Neuroimmunol. 2001 Oct 1;119(2):166-74
11585618
Genes Immun. 2002 Aug;3(5):279-85
12140746
Hum Mol Genet. 2002 Sep 15;11(19):2251-6
12217953
Genes Immun. 2002 Dec;3(8):464-9
12486604
Nat Genet. 2003 Jan;33(1):25-32
12461526
Bioinformatics. 2003 May 1;19(7):889-90
12724300
Eur J Immunol. 2003 Jul;33(7):1907-16
12811851
Scand J Immunol. 2004 Jul-Aug;60(1-2):39-51
15238072
J Immunol. 2004 Jul 15;173(2):1366-73
15240732
Lancet. 1973 Dec 1;2(7840):1221-5
4128558
N Engl J Med. 1986 Dec 25;315(26):1638-42
3785335
Am J Pathol. 1988 Mar;130(3):443-54
2450462
Genetics. 1989 Jan;121(1):185-99
2563713
J Immunol. 1991 Mar 1;146(5):1490-5
1899688
Nucleic Acids Res. 1991 Aug 11;19(15):4293
1870982
Tissue Antigens. 1991 Jul;38(1):1-15
1926129
Ann Neurol. 1993 Mar;33(3):281-5
8498811
J Clin Invest. 1993 Dec;92(6):2602-8
7504688
Genetics. 1994 Nov;138(3):963-71
7851788
Nat Genet. 1995 Jan;9(1):63-9
7704027
Arterioscler Thromb Vasc Biol. 2000 Jan;20(1):223-9
10634822