Figure 3.

Presenilin-deficient Ngn3-derived progenitors proliferate at a sustained rate and turn over rapidly in the adult. (A) Quantification of the percentage of Phospho-Histone3-positive cells in control and Presenilin-deficient mice at E18.5 (n = 25), newborn mice (n = 24), and adult mice (n = 25). More than 3900 nuclei were counted for each mouse. Presenilin-deficient mice display an increased proliferation rate at all stages. Gray bars represent SEM; (*) P < 0.05; (**) P < 0.01. (B) Western-blot analysis for the expression of Cyclins D1, D2, and D3 in total pancreatic extracts of control (Ngn3-Cre; Z/EG) and Presenilin-deficient (Ngn3-Cre; Ps1^+/f; Ps2^−/−; Z/EG and Ngn3-Cre; Ps1^f/−; Ps2^−/−; Z/EG). The immunoblots are normalized over actin and indicate that Cyclin D3 increased concomitantly with the reduction of Presenilins. (C) Expression of Ngn3 around forming islets at E18.5 in control (panel 1) and Presenilin-deficient (panel 2) mice. Ngn3 is stained in red and insulin is stained in green. Bars, 50 μm. (D) Overall proportion of Ngn3⁺ cells is represented on the right. Gray bars represent SEM; P < 0.05. (E) Quantification of the percentage of TUNEL-positive cells in control and Presenilin-deficient mice at E18.5 (n = 23), newborn mice (n = 24), and adult mice (n = 24); >3400 nuclei were counted for each mouse. The apoptosis rate is indistinguishable between control and Presenilin-deficient mice at E18.35 and at birth, but increases in Presenilin mice in the adult. Gray bars represent SEM; P < 0.05.