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Figure 1—source data 1. Albuminuria in parental, consomic, and congenic rat strains.

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Figure 4. Validation of differentially expressed genes in isolated glomeruli by quantitative real-time PCR (qPCR) analysis. ; (A) qPCR analysis showed no consistent differential expression for eight genes from overall 10 genes identified with differential expression in RNA sequencing (RNA-Seq) analysis (Table 3) between parental Munich Wistar Frömter (MWF), spontaneously hypertensive rats (SHR), and consomic MWF-6SHR during the crucial time window for onset of albuminuria between weeks 4 and 8. Only transmembrane protein 63c (Tmem63c) demonstrated differential mRNA expression at both time points. Acyl-CoA thioesterase 3 (Acot3) (Table 3) showed very low mRNA expression in qPCR analysis precluding quantitative analysis. Consequently, Acot3 and the genes shown were excluded from and Tmem63c was included for further functional analysis. Rats per strain (n = 7–8, each); values for Acot5 (week 8),Tgfb3 (week 4) and Tmem63c (week 8) are plotted as median ±IQR, while the rest of data are plotted as mean ±SD; data for Acot5 (week 8), Tgfb3 (week 4) and Tmem63c (week 8) were analyzed using Kruskal-Wallis test with Dunn’s post-hoc analysis and Mann-Whitney U test, while the rest of data was analyzed by one-way ANOVA with Bonferroni’s post hoc analysis and Mann-Whitney U test. (B) mRNA expression analysis for Tmem63c in isolated glomeruli by qPCR analysis is shown for MWF, SHR, congenic MWF.SHR-(D6Rat1-D6Mgh4) (Rat1-Mgh4) and congenic MWF.SHR-(D6Rat1-D6Rat81) (Rat1-Rat81), at week 4 and week 8. Rats per strain (n = 6–8, each); data for week 8 are plotted as median ±IQR and analyzed using Kruskal-Wallis test with Dunn’s post hoc analysis and Mann-Whitney U test; the other data are plotted as mean ±SD and analyzed by one-way ANOVA with Bonferroni’s post hoc analysis and Mann-Whitney U test (C) Representative immunohistochemical stainings of TMEM63C and Wilms tumor 1 (WT1) on kidney sections from SHR and MWF at 8 weeks of age; the insert indicates expression in podocytes. Scale bar = 50 µm. Quantitative analysis of TMEM63C intensity in podocytes using one-way ANOVA revealed lower intensity in MWF (n = 7) vs. SHR (n = 6) at 8 weeks (p=0.0032).

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Figure 1. Congenic substitution mapping of the albuminuria and nephron deficit QTL on rat chromosome 6. ; (A) Urinary albumin excretion (UAE) in Munich Wistar Frömter (MWF) and spontaneously hypertensive rats (SHR) at 8 weeks of age. MWF (n = 18); SHR (n = 10); values plotted: median ±interquartile range (IQR); Mann-Whitney U test; *p

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Figure 1—figure supplement 2. Renal-specific Tfeb overexpression results in kidney enlargement and failure. ; (A) Tamoxifen injection of Cdh16CreErt2::Tfebfs mice at P12, P14 and P30 with representative images at the time of sacrifice (tam, tamoxifen). (B) Relative ratio of kidney to body weight (KW/BW) evaluated in tam-treated Cdh16CreErt2::Tfebfs mice at P90. Two-way Anova was applied (factors: treatment, genotype). (C) Blood urea and albuminuria levels in Cdh16Cre::Tfebfs and Cdh16CreErt2::Tfebfs mice. Values are shown as means (± SEM) of at least three Cdh16Cre::Tfebfs and Cdh16CreErt2::Tfebfs mice and are normalized versus the control animals (Cdh16Cre and Cdh16CreErt2). (D) High-frequency ultrasound (HFUS) images of kidneys from P30 Cdh16Cre::Tfebfs mice. (E) Images and PAS staining from tam-treated Cdh16CreErt2::Tfebfs mice at P90.

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Analysis of the genomic architecture of a complex trait locus in hypertensive rat models links Tmem63c to kidney damage

• Authors : Schulz, Angela; Müller, Nicola Victoria; van de Lest, Nina Anne ...

• Source: eLife ; volume 8 ; ISSN 2050-084X

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Empagliflozin reduces podocyte lipotoxicity in experimental Alport syndrome

• Authors : Ge, Mengyuan; Molina, Judith; Kim, Jin-Ju ...

• Source: eLife ; volume 12 ; ISSN 2050-084X

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