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Journal: The EMBO Journal

Article Title: Functional rescue of a disease-linked ERAD pathway mutation via alternative splicing

doi: 10.1038/s44318-026-00757-5

Figure Lengend Snippet: ( A ) The survival rate of WT, HET and KI pups at postnatal day 0 (p0). Observed vs. Expected * P = 0.013. ( B ) Body weight at p0. n = 7–9 mice/group. WT vs. KI, P = 0.94. ( C ) The photo of pups at postnatal 4 h (upper) and >12 h (lower). Scale bars: 1 cm. ( D ) Tissue morphology of SEL1L C141Y KI pups at P0, with tissue weight quantification shown below. n = 7–9 mice/group. Scale bars: 1 cm. WT vs. KI, Liver P = 0.45, Brain P = 0.65, Thymus P = 0.14, Spleen P = 0.16. ( E ) Morphology of postprandial stomach in the P0 WT and KI pup, with quantification shown on the right. n = 7–9 mice/group. Scale bars : 1 cm. WT vs. KI, **** P = 0.000013. ( F ) The survival curve of WT, HET and KI pups after birth. n = 17–41 mice/group. WT vs. HET, P = 0.86; WT vs. KI, **** P < 0.0001. ( G ) Body weight growth of male and female WT, HET, KI’ mice for postnatal week 1 to week 10. n = 3–20 mice/group. ( H ) Quantification of B cells as a percentage of CD45⁺ peripheral blood mononuclear cells (PBMCs) at p0 by flow cytometry in Fig. . n = 5–10 mice/group. WT vs. KI, *** P = 0.0002; WT vs. KI’, P = 0.63; KI vs. KI’, ** P = 0.0091. ( I , J ) Hematoxylin and eosin (H&E) staining and Immunofluorescence of CD19 + B cells in p0 mouse spleens from SEL1L C141Y KI pups at p0, with quantification shown in ( J ). Red, CD19; Blue, DAPI. n = 3 mice/group. Scale bars: 50 μm for zoom-out photo, 20 μm for zoom-in photo and immunofluorescence figure. *** P = 0.0026. Data are represented as means ± SEM. n.s. not significant. * P < 0.05; ** P < 0.01; *** P < 0.001, **** P < 0.0001, by Chi-square test for ( A ); two-tailed t test for ( B , D , E , J ); Mantel–Cox test for ( F ); two-way ANOVA followed by Tukey’s multiple-comparisons test for ( G ); one-way ANOVA followed by Tukey’s post hoc test for ( H ). .

Article Snippet: ProLongTM Diamond Antifade Mountant with DAPI , Fisher Scientific , P36971.

Techniques: Flow Cytometry, Staining, Immunofluorescence, Two Tailed Test

Journal: The EMBO Journal

Article Title: Functional rescue of a disease-linked ERAD pathway mutation via alternative splicing

doi: 10.1038/s44318-026-00757-5

Figure Lengend Snippet: ( A – C ) Western blot analysis of SEL1L protein expression ( A ), HRD1 and ERAD substrate IRE1α ( B ) in mouse brains or cortex at indicated ages, with quantification in ( C ). n = 3–4 mice/group. SEL1L: WT vs. HET, P = 0.057; WT vs. KI, *** P = 0.0006; HRD1: WT vs. HET, P = 0.52; WT vs. KI, ** P = 0.0017; IRE1α: WT vs. HET, P = 0.99; WT vs. KI, **** P < 0.0001. ( D , E ) Western blot analysis ( D ) of ERAD protein and ERAD substrates from WT and KI’ mice brain with quantification shown in ( E ). n = 3–4 mice/group. SEL1L: WT vs. KI’, *** P = 0.0009; HRD1: WT vs. KI’, P = 0.34; IRE1α: WT vs. KI’, P = 0.28. ( F ) Phos-tag gel analysis of IRE1α phosphorylation in p0 WT, HET and KI brains. n = 3–4 mice/group. ( G ) RT-PCR analysis of Xbp1 mRNA splicing of p0 WT, KI, and KI’ brains with quantification in Fig. . n = 3–6 mice/group, 3–4 for positive controls. u, unspliced. s, spliced. ( H , I ) Immunofluorescence ( H ) of SATB2+ Layer II/III cells and the CTIP2+ Layer V in the cortex of p0 WT, KI and KI’ mice, with zoom-in region showing SATB2+ cells below Layer V and with quantification shown in ( I ). n = 3–6 mice/group. Green, CTIP2; Red, SATB2; Blue, DAPI. WT vs. KI, * P = 0.046; WT vs. KI’, * P = 0.032; KI vs. KI’, *** P = 0.0007. Data are represented as means ± SEM. n.s. not significant. * P < 0.05; ** P < 0.01; *** P < 0.001, **** P < 0.0001, by one-way ANOVA followed by Tukey’s post hoc test for ( C , I ); two-tailed t test for ( E ). .

Article Snippet: ProLongTM Diamond Antifade Mountant with DAPI , Fisher Scientific , P36971.

Techniques: Western Blot, Expressing, Phospho-proteomics, Reverse Transcription Polymerase Chain Reaction, Immunofluorescence, Two Tailed Test