Fig. 6: Human 15q13.3 microdeletion patient iNeurons display impairments in axon growth and intrinsic excitability. | Molecular Psychiatry

Fig. 6: Human 15q13.3 microdeletion patient iNeurons display impairments in axon growth and intrinsic excitability.

From: Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome

Fig. 6

a Confocal images of PNI day 10 Venus-transfected Control and 15q13.3 HET iNeurons. 20× objective, tiled and stitched. Scale bar = 100 µm. b Quantification of axon length in Family 1 and OTUD7AL233F/L233F iNeurons. n = 39 neurons Control Fam 1, n = 34 neurons 15q13.3 HET Fam 1, n = 26 neurons OTUD7AL233F/L233F; *p < 0.05, one-way ANOVA with Dunnett’s post hoc test, F (2, 96) = 3.306, p = 0.0409. c Quantification of axon length in Family 2 iNeurons. n = 23 neurons Control Fam 2, n = 34 neurons 15q13.3 HET Fam 2 carrier, and n = 28 neurons 15q13.3 HET proband Fam 2. ***p < 0.001, one-way ANOVA with Dunnett’s post hoc test, F (2, 82) = 7.021, p = 0.0015. d Quantification of axon length in Family 3 iNeurons. n = 24 neurons Control Fam 3, n = 13 15q13.3 HET. *p < 0.05, Unpaired t-test (two-tailed), t = 2.614, df = 35, p = 0.0131. e, f Family 1 and OTUD7AL233F/L233F iNeuron intrinsic membrane properties. e Rheobase (Kruskal–Wallis test with Dunn’s post hoc test; Kruskal–Wallis statistic = 0.1493, p = 0.9281 approximate; Control (Fam 1): n = 32 neurons, 15q13.3 HET (Fam 1): n = 38 neurons, OTUD7AL233F/L233F: n = 24 neurons) and f action potential threshold (**p < 0.01, one-way ANOVA with Dunnett’s post hoc test; F (2, 93) = 4.372, p = 0.0153); Control (Fam 1): n = 32 neurons, 15q13.3 HET (Fam 1): n = 38 neurons, OTUD7AL233F/L233F: n = 23 neurons. g Representative traces of action potentials evoked by 60 pA of injected current in PNI day 26–28 Family 1 and OTUD7AL233F/L233F patient human iNeurons. h Repetitive firing properties of PNI day 26–28 Family 1 and OTUD7AL233F/L233F patient human iNeurons. Two-way ANOVA with Dunnett’s post hoc test. Interaction: F (14, 325) = 0.4370, p = 0.9620; Injected current: F (7, 325) = 74.84, p < 0.0001; Genotype: F (2, 325) = 0.2437, p = 0.7838. i, j Family 2 Intrinsic membrane properties. i Rheobase (*p < 0.05, one-way ANOVA with Tukey’s post hoc test, F (2, 73) = 4.730, p = 0.0117) and j action potential threshold (one-way ANOVA with Tukey’s post hoc test, F (2, 68) = 0.3923, p = 0.6770). Control (Fam 2): n = 24 neurons, 15q13.3 HET Carrier (Fam 2): n = 26 neurons, 15q13.3 HET Proband (Fam 2): n = 26 neurons. k Representative traces of action potentials evoked by 100 pA of injected current in PNI day 26–28 Family 2 human iNeurons. l Repetitive firing properties of PNI day 26–28 Family 2 human iNeurons. *p < 0.05, **p < 0.01, ***p < 0.001, two-way ANOVA with Dunnett’s post hoc test. Interaction: F (24, 666) = 1.253, p = 0.1879; Injected current: F (12, 666) = 75.03, p < 0.0001; Genotype: F (2, 666) = 32.16, p < 0.0001. Control (Fam 2): n = 24 neurons, 15q13.3 HET Carrier (Fam 2): n = 25 neurons, 15q13.3 HET Proband (Fam 2): n = 23 neurons. m, n Family 3 Intrinsic membrane properties. m Rheobase (*p < 0.05, Mann–Whitney test two-tailed, Mann–Whitney U = 271, p = 0.0180; Control: 110.0 median, n = 29 neurons, 15q13.3 HET: 120.0 median, n = 29 neurons) and n action potential threshold (*p < 0.05, unpaired t-test two-tailed; t = 2.347, df = 57, p = 0.0224; Control: n = 30 neurons, 15q13.3 HET: n = 29 neurons). o Representative traces of action potentials evoked by 100 pA of injected current in PNI day 26–28 Family 3 human iNeurons. p Repetitive firing properties of PNI day 26–28 Family 3 human iNeurons. Two-way ANOVA with Sidak’s post hoc test; Interaction: F (15, 603) = 0.7090, p = 0.7766; Injected current: F (15, 603) = 78.61, p < 0.0001; Genotype: F (1, 603) = 21.41, p < 0.0001.

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