Fig. 4: Induction of TBL/R1 loss of function in adult β-cells produces progressive diabetes due to impaired maintenance of β-cell identity.
From: TBL1X/TBL1XR1 govern β-cell identity through a PAX6-containing gene regulatory network
a Scheme for the generation of an inducible β-cell-specific TBL1X and TBL1XR1 knockout. b Random fed blood glucose levels over time in iTBL/RβKO (n = 9) and control (n = 9) mice on HFD. c Total pancreas insulin content normalized to protein levels in iTBL/RβKO and control mice 4 and 11 weeks after tamoxifen administration. n = 3 for 4w control and iTBL/RβKO mice, n = 6 for 11w control mice, n = 4 for 11w iTBL/RβKO mice. d, e Blood glucose (d) and plasma insulin (e) levels during an oral glucose tolerance test after 22 weeks of HFD. Corresponding area under the curve in iTBL/RβKO (n = 8) and control (n = 9) mice (d, right). f, g Relative mRNA expression determined by qPCR in pancreatic islets of iTBL/RβKO and control mice of Tbl1x and Tbl1xr1 (f) and islet genes (g). Control mice Tbl1x, Tbl1xr1, Ins1, Ins2, Nkx6.1, Slc2a2, Mafa, Pdx1, Pax6, Ucn3: n = 9, control mice ChgA, Ngn3, Ldha, Hk1: n = 8, iTBL/RβKO mice Tbl1x, Ngn3, Ldha, Hk1: n = 7, iTBL/RβKO mice Tbl1xr1, Ins1, Ins2, Slc2a2, Mafa n = 6, iTBL/RβKO mice Nkx6.1, Pdx1, Pax6, Ucn3, ChgA: n = 5. h α/β-cell mass ratio of pancreatic islets from iTBL/RβKO (n = 4) and control mice (n = 4) on HFD, 24 weeks after knockout induction. i Representative immunofluorescent staining of insulin+ (blue, β-cells) and glucagon+ (red, α-cells) cells of paraffin-embedded pancreas from iTBL/RβKO and control mice on HFD, 24 weeks after knockout induction. Each point represents one mouse. Data are represented as mean ± SEM. The following statistical tests were applied: two-sided student’s t test (d – Area under the curve, f–h) and 2-way ANOVA with Šidák’s multiple comparison post hoc test (b–d – time course, e). Source data are provided as a Source Data file.
