The NOD Idd9 genetic interval influences the pathogenicity of insulitis and contains molecular variants of Cd30, Tnfr2, and Cd137.
Previous analyses of NOD mice have shown that some genes control the development of both insulitis and diabetes, while other loci influence diabetes without reducing insulitis. Evidence for the existence of a gene only influencing diabetes, Idd9 on mouse chromosome 4, is provided here by the development of a novel congenic mouse strain, NOD.B10 Idd9. NOD.B10 Idd9 mice display profound resistance to diabetes even though nearly all develop insulitis. Subcongenic analysis has demonstrated that alleles of at least three B10 genes, Idd9.1, Idd9.2, and Idd9.3 are required to produce Idd9-mediated diabetes resistance. Candidate genes with amino acid differences between the NOD and B10 strains have been localized to the 5.6 cM Idd9.2 interval (Tnfr2, Cd30) and to the 2.0 cM Idd9.3 interval (Cd137).
The Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge University, United Kingdom.
P A
PA
Lyons
W W
WW
Hancock
P
P
Denny
C J
CJ
Lord
N J
NJ
Hill
N
N
Armitage
T
T
Siegmund
J A
JA
Todd
M S
MS
Phillips
J F
JF
Hess
S L
SL
Chen
P A
PA
Fischer
L B
LB
Peterson
L S
LS
Wicker
D000483:Alleles; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D014644:Genetic Variation; D007328:Insulin; D007515:Islets of Langerhans / Q000276:immunology; D017730:Ki-1 Antigen / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D005810:Multigene Family; D010195:Pancreatitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D015703:Antigens, CD; D007328:Insulin; D017730:Ki-1 Antigen; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9