Aod1, the immunoregulatory locus controlling abrogation of tolerance in neonatal thymectomy-induced autoimmune ovarian dysgenesis, maps to mouse chromosome 16.
Mice thymectomized at three days of age (D3Tx) develop during adulthood a variety of organ-specific autoimmune diseases, including autoimmune ovarian dysgenesis (AOD). The phenotypic spectrum of AOD is characterized by the development of anti-ovarian autoantibodies, oophoritis, and atrophy. The D3Tx model of AOD is unique in that disease induction depends exclusively on perturbation of the normal developing immune system, is T-cell-mediated, and is strain specific. For example, D3Tx A/J mice are highly susceptible to AOD, whereas C57BL/6J mice are resistant. After D3Tx, self ovarian antigens, expressed at physiological levels, trigger an autoimmune response capable of eliciting disease. The D3Tx model provides, therefore, the opportunity to focus on the mechanisms of self-tolerance that are relevant to disease pathogenesis. Previous studies indicate that the principal mechanisms involved in AOD susceptibility are genetically controlled and govern developmental processes associated with the induction and maintenance of peripheral tolerance. We report here the mapping of the Aod1 locus to mouse chromosome 16 within a region encoding several loci of immunologic relevance, including scid, Igl1, VpreB, Igll, Igl1r, Mtv6 (Mls-3), Ly-7, Ifnar, and Ifgt.
Wardell
B B
BB
Department of Microbiology, Brigham Young University, Provo, UT 84602, USA.
Michael
S D
SD
Tung
K S
KS
Todd
J A
JA
Blankenhorn
E P
EP
McEntee
K
K
Sudweeks
J D
JD
Hansen
W K
WK
Meeker
N D
ND
Griffith
J S
JS
D000818:Animals; D001284:Atrophy; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D008040:Genetic Linkage; D006059:Gonadal Dysgenesis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance / Q000235:genetics*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D010049:Ovarian Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010053:Ovary / Q000276:immunology / Q000473:pathology; D012016:Reference Values; D013934:Thymectomy