Fractional and absolute volumes of cortex and medulla in the kidney of homozygous (HOM) and heterozygous (HET) <i>Pou3f3</i>^<i>L423P</i> mutant mice and control (CON) mice at 60 weeks of age.

<p>Fractional and absolute volumes of cortex and medulla in the kidney of homozygous (HOM) and heterozygous (HET) <i>Pou3f3</i>^<i>L423P</i> mutant mice and control (CON) mice at 60 weeks of age.</p

Quantitative stereological data of glomeruli in homozygous (HOM) and heterozygous (HET) Pou3f3^L423P mutant mice and control (CON) mice at 12 days of age.

<p>Quantitative stereological data of glomeruli in homozygous (HOM) and heterozygous (HET) Pou3f3^L423P mutant mice and control (CON) mice at 12 days of age.</p

Quantitative stereological data of glomeruli and glomerular subcompartments in homozygous (HOM) and heterozygous (HET) <i>Pou3f3</i>^<i>L423P</i> mutant mice and control (CON) mice at 60 weeks of age.

<p>Quantitative stereological data of glomeruli and glomerular subcompartments in homozygous (HOM) and heterozygous (HET) <i>Pou3f3</i>^<i>L423P</i> mutant mice and control (CON) mice at 60 weeks of age.</p

Kidney histology of 12-day-old and of 60-week-old homozygous (HOM) and heterozygous (HET) <i>Pou3f3</i>^<i>L423P</i> mutant mice and non-mutant control mice (CON).

<p>GMA/MMA sections, HE staining. Bars = 100 μm, in insets = 50 μm.</p

Fractional and absolute volumes of cortex and medulla in the kidney of homozygous (HOM) and heterozygous (HET) <i>Pou3f3</i>^<i>L423P</i> mutant mice and control (CON) mice at 12 days of age.

<p>Fractional and absolute volumes of cortex and medulla in the kidney of homozygous (HOM) and heterozygous (HET) <i>Pou3f3</i>^<i>L423P</i> mutant mice and control (CON) mice at 12 days of age.</p

SDS-PAGE urine protein analysis of 60-week-old homozygous (HOM) and heterozygous (HET) <i>Pou3f3</i>^<i>L423P</i> mutant mice and non-mutant control (CON) mice.

<p>A representative gel of individual spot urine samples of three male and female HOM, HET and CON mice diluted to identical creatinine concentrations is shown. Molecular weight marker (M), murine serum albumin (ALB). Mice of all examined genotypes display discrete albumin bands (arrow) at approximately 67 kDa. The intensity of the major urinary protein (MUP) bands at approximately 18–25 kDa in male mice is stronger than in female mice.</p

True harmonic mean thickness of the glomerular basement membrane (GBM) and filtration slit frequency (FSF) in homozygous (HOM) and heterozygous (HET) <i>Pou3f3</i>^<i>L423P</i> mutant mice and control (CON) mice at 60 weeks of age.

<p>True harmonic mean thickness of the glomerular basement membrane (GBM) and filtration slit frequency (FSF) in homozygous (HOM) and heterozygous (HET) <i>Pou3f3</i>^<i>L423P</i> mutant mice and control (CON) mice at 60 weeks of age.</p

Verification of DEGs, identified by transcriptome profiling of whole kidneys, by RT-qPCR.

<p>Data are shown as scatter dot plot with mean (n = 5 per group). Age of mice analyzed: four months. One-way-ANOVA with Tukey's Multiple Comparison Post hoc Test: <i>p</i> vs. wild-type, *, <i>p</i><0.05; **, <i>p</i><0.01; ***, p<0.001.</p

Analysis of localization and protein abundance of ANGPTL7 in healthy and UAKD-affected kidneys.

<p>(<b>A</b>) ANGPTL7 was predominantly detected in the cytoplasmic compartment of tubular cells, predominantly in TALH cells, of wild-type mice. Compared to the staining intensity of ANGPTL7 in TALH cells of wild-type mice, TALH cells of <i>Umod</i> mutant mice exhibited a lower cytoplasmic staining intensity of ANGPTL7. Age of mice analyzed: four months. <i>Umod</i>^wt: wild-type mouse; <i>Umod</i>^C93F: homozygous <i>Umod</i>^C93F mutant mouse. UMOD immunohistochemistry enabled identification of TALH segments. Serial kidney sections were used for ANGPTL7 and uromodulin immunohistochemistry and corresponding kidney regions are shown. C: renal cortex; P: renal papilla. Chromogen: DAB; nuclear staining: hemalum. (<b>B</b>) Protein abundance of ANGPTL7 in the outer medulla of kidneys of homozygous <i>Umod</i> mutant mice of both lines was decreased compared to wild-type mice. Signal intensities of ANGPTL7 were corrected for GAPDH signal intensities of the same PVDF-membrane. Mean of protein abundance of wild-type mice was set on a value of 1 [mean (wild-type)  = 1]. One-way-ANOVA with Tukey's Multiple Comparison Post hoc Test: <i>p</i> vs. wild-type, **, <i>p</i><0.01; ***, p<0.001. Age of mice analyzed: four months.</p

Analysis of localization and protein abundance of SCD1 in healthy and UAKD-affected kidneys.

<p>(<b>A</b>) SCD1 was detected in the cytoplasmic compartment selectively of proximal tubular cells (in the straight S3 segment). In the kidney of the homozygous <i>Umod</i>^C93F mutant mouse, SCD1 appeared to be abundant in a larger fraction of proximal tubular cells compared to the kidney of the wild-type mouse, and the average staining intensity of SCD1 positive cells appeared to be more prominent. Age of mice analyzed: four months. <i>Umod</i>^wt: wild-type mouse; <i>Umod</i>^C93F: homozygous <i>Umod</i>^C93F mutant mouse. Uromodulin immunohistochemistry enabled identification of TALH segments. Proximal tubule segment are morphologically characterized by luminal microvilli. Chromogen: DAB for SCD1, Vector RED for UMOD; nuclear staining: hemalum. (<b>B</b>) Protein abundance of SCD1 in whole kidney lysate of homozygous <i>Umod</i> mutant mice of both lines was increased compared to wild-type mice. Signal intensities of SCD1 were corrected for GAPDH signal intensities of the same PVDF-membrane. Mean of protein abundance of wild-type mice was set on a value of 1 [mean (wild-type)  = 1]. One-way-ANOVA with Tukey's Multiple Comparison Post hoc Test: <i>p</i> vs. wild-type, **, <i>p</i><0.01; ***, p<0.001. Age of mice analyzed: four months.</p