Figure 5.

Residual NTE activity dictates the onset of retinopathy and embryonic lethality in PNPLA6 missense allelic series mice. (A) Predicted overall neuropathy target esterase (NTE) activity of allelic series mice using human in vitro variant activities (Fig. 2). (B) The proportion of viable homozygous pups in the PNPLA6 allelic series. The red line denotes the normal Mendelian ratio expected (25%). See Supplementary Table 2 for exact numbers. (C) NTE activity of viable homozygous allelic series mice brain homogenate. (D) Six-month scotopic electroretinogram (ERG) wave amplitudes at a stimulus intensity of 10 cd.s/m². (E) Six-month photopic ERG wave amplitudes at a stimulus intensity of 100 cd.s/m². (F) Total retinal thickness measured from spectral domain-optical coherence tomography (SD-OCT) images at 6 months. Box and whisker plots extend from the 25th to 75th percentiles, with whiskers extending to the minimum and maximum values in the dataset. The median is the line plotted between boxes. D–F used one-way ANOVA with post hoc Tukey test with α=0.05. P > 0.05 (not significant, ns), *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Significant values in D–F indicate significance between Control and MV/GS values. See Supplementary material, ‘Supporting data values’ file for exact mean, n and standard deviation values.