Fig. 7: In vivo selective deletion of GDF11 in excitatory neurons induced their own senescence requires p21.
From: GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21
a, b Genetic strategy for generation of p21f/f mice (a) and CaMKIIα-Cre; GDF11f/f; p21f/f mice (b) to selectively delete both GDF11 and p21 in CaMKIIα+ neurons through Cre/Loxp system. c–g Representative images (c) and quantification (d–g) of the SA-β-Gal+ cells in the cingulate cortex (c, up, and d, n = 4 per group), layers 4 and 5 (c, middle, and e GDF11f/f, n = 4; GDF11cKO, n = 3; CaMKIIα-Cre; GDF11f/f;p21f/f, n = 5), layer 6a (c middle, and f layer 6a is the deep layer cortex near the corpus callosum (CC), GDF11f/f, n = 5; GDF11cKO, n = 4; CaMKIIα-Cre; GDF11f/f;p21f/f, n = 4) of the insular cortex (IC), and layers 2 and 3 of the piriform cortex (c down, and g the dashed lines indicate the borders of layers 2 and 3, GDF11f/f, n = 8; GDF11cKO, n = 4; CaMKIIα-Cre; GDF11f/f;p21f/f, n = 8) of CaMKIIα-Cre; GDF11f/f;p21f/f or GDF11cKO or GDF11f/f mice aged 17 M. Examples of the SA-β-Gal+ cells are indicated by double arrows. Scale bars, as shown on the images, 50 μm (c, up and middle) and 20 μm (c, middle and down). Data are presented as mean ± SEM. *P < 0.05, **P < 0.01. d (F (2, 9) = 72.52, P < 0.0001; GDF11f/f versus GDF11cKO, P = 0.0006; GDF11cKO versus CaMKIIα-Cre;GDF11f/f;p21f/f, P < 0.0001; GDF11f/f versus CaMKIIα-Cre;GDF11f/f;p21f/f, P = 0.0004), e (F (2, 9) = 78.16, P < 0.0001; GDF11f/f versus GDF11cKO, P = 0.0020; GDF11cKO versus CaMKIIα-Cre;GDF11f/f;p21f/f, P < 0.0001; GDF11f/f versus CaMKIIα-Cre;GDF11f/f;p21f/f, P < 0.0001), f (F (2, 10) = 49.87, P < 0.0001; GDF11f/f versus GDF11cKO, P < 0.0001; GDF11cKO versus CaMKIIα-Cre;GDF11f/f;p21f/f, P < 0.0001; GDF11f/f versus CaMKIIα-Cre;GDF11f/f;p21f/f, P = 0.0347) and g (F (2, 17) = 102.8, P < 0.0001; GDF11f/f versus GDF11cKO, P = 0.0227; GDF11cKO versus CaMKIIα-Cre;GDF11f/f;p21f/f, P < 0.0001; GDF11f/f versus CaMKIIα-Cre;GDF11f/f;p21f/f, P = 0.0001), One-way ANOVA with post Tukey multiple comparisons test. Source data are provided with this paper.
