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. 2022 Nov 5;66:101632. doi: 10.1016/j.molmet.2022.101632

Figure 1.

Figure 1

Acceleration of type 1 diabetes in NOD. ZnT8 knockout mice. (A) Representative islet images using immunofluorescent staining of DAPI (blue), ZnT8 (green), and insulin (red) from 12wk NOD. ZnT8 wild-type mice and 7wk NOD. ZnT8 Heterozygote and NOD. ZnT8 knockout mice. Scale bars: 75 μm. (B) Female mice were monitored for the appearance of spontaneous T1D. Median survival was 112 days (KO), 145 days (HE, p < 0.001 vs KO), and 137.5 days (WT, p = 0.0113 vs KO, 0.046 vs HE). Incidence was 97% (KO), 76% (HE), and 93% (WT) by 40 weeks. (C) Age dependent intraperitoneal glucose tolerance test (IPGTT) after 16 h fasting. HE (blue) and KO (red). (6∼8wks: n = 30 KO, n = 36 HE; 8–10wks: n = 43 KO, n = 46 HE; 10–12wks: n = 36 KO, n = 30 HE; 12–14wks: n = 50 KO, n = 45 HE; 14–16wks: n = 33 KO, n = 25 HE). Data are expressed as the mean ± SEM. ∗p < 0.05, ∗∗∗∗p < 0.0001; Mann–Whitney U test. (D, E) H & E stained pancreas sections from 7 to 8wk NOD. ZnT8 HE and NOD. ZnT8 KO mice were examined in a blinded fashion for evidence of insulitis. (D) 111 islets from 9 NOD. ZnT8 HE mice and 398 islets from 10 NOD. ZnT8 knockout mice were examined. The frequency of islets with any evidence of insulitis was calculated. Data are expressed as the mean ± SEM. ∗p = 0.02; Mann–Whitney U test. (E) Representative H&E images of the most highly infiltrated islets from HE (upper) and KO (lower) animals.