Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire
J. Clin. Invest. Maureen A. Su, et al. 118:1712 doi:10.1172/JCI34523 [
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Figure 3NOD.GW/+ mice develop dominant autoimmune disease that is distinct from that of
NOD.+/o and
NOD.o/o.
(
A) Infiltration scores of
NOD.+/+,
NOD.+/o,
NOD.GW/+,
NOD.GW/o, and
NOD.o/o cohorts at 10 (top) and 25–30 weeks (bottom) for organs indicated. Each circle represents an individual mouse. Bars indicate average infiltrate score for each cohort. **
P ≤ 0.001 compared with both
Aire+/+ and
Aire+/o. NA, not available due to death. (
B) Top: Thyroid infiltrate scores of 15- to 25-week-old mice in the NOD background of given genotype. Each circle represents an individual mouse. Bottom: H&E-stained sections (original magnification, ×5) of thyroid gland from 20-week-old
NOD.+/+ (left) and
NOD.GW/+ (right) mice. (
C) Top: H&E-stained sections (original magnification, ×20) of sciatic nerve from 25-week-old
NOD.+/+ (left) and
NOD.GW/+ (right) littermates. Bottom: H&E-stained pancreas sections (original magnification, ×5) from
NOD.o/o (left),
NOD.GW/+ (middle), and
NOD.GW/o (right). Arrows point to islets; arrowhead points to intra-islet infiltration. (
D) Percentage of activated CD4
+ splenocytes (CD62L
lo, CD44
hi) in 6- to 10-week-old mice of given genotype in the NOD background by flow cytometry. Averages ± SD of 5 independent experiments are shown. **
P ≤ 0.03 compared with both
NOD.+/+ and
NOD.+/o. (
E) Weight curves of
NOD.+/+ (
n = 10),
NOD.GW/+ (
n = 11), and
NOD.GW/o (
n = 4) cohorts, showing average weight ± SD. (
F) Neuropathy (red squares) and diabetes (blue circles) incidence curves of
NOD.+/+ (
n = 10, open symbols) and
NOD.GW/+ (
n = 11, filled symbols) littermates. *
P = 0.0035, difference in neuropathy between
NOD.+/+ and
NOD.GW/+ mice.
