Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-72 |
Sentence |
denotes |
An inducible mouse model of podocin-mutation-related nephrotic syndrome. |
T2 |
73-156 |
Sentence |
denotes |
Mutations in the NPHS2 gene, encoding podocin, cause hereditary nephrotic syndrome. |
T3 |
157-286 |
Sentence |
denotes |
The most common podocin mutation, R138Q, is associated with early disease onset and rapid progression to end-stage renal disease. |
T4 |
287-443 |
Sentence |
denotes |
Knock-in mice carrying a R140Q mutation, the mouse analogue of human R138Q, show developmental arrest of podocytes and lethal renal failure at neonatal age. |
T5 |
444-632 |
Sentence |
denotes |
Here we created a conditional podocin knock-in model named NPHS2 R140Q/-, using a tamoxifen-inducible Cre recombinase, which permits to study the effects of the mutation in postnatal life. |
T6 |
633-751 |
Sentence |
denotes |
Within the first week of R140Q hemizygosity induction the animals developed proteinuria, which peaked after 4-5 weeks. |
T7 |
752-856 |
Sentence |
denotes |
Subsequently the animals developed progressive renal failure, with a median survival time of 12 (95% CI: |
T8 |
857-870 |
Sentence |
denotes |
11-13) weeks. |
T9 |
871-994 |
Sentence |
denotes |
Foot process fusion was observed within one week, progressing to severe and global effacement in the course of the disease. |
T10 |
995-1119 |
Sentence |
denotes |
The number of podocytes per glomerulus gradually diminished to 18% compared to healthy controls 12-16 weeks after induction. |
T11 |
1120-1223 |
Sentence |
denotes |
The fraction of segmentally sclerosed glomeruli was 25%, 85% and 97% at 2, 4 and 8 weeks, respectively. |
T12 |
1224-1382 |
Sentence |
denotes |
Severe tubulointerstitial fibrosis was present at later disease stage and was correlated quantitatively with the level of proteinuria at early disease stages. |
T13 |
1383-1516 |
Sentence |
denotes |
While R140Q podocin mRNA expression was elevated, protein abundance was reduced by more than 50% within one week following induction. |
T14 |
1517-1646 |
Sentence |
denotes |
Whereas miRNA21 expression persistently increased during the first 4 weeks, miRNA-193a expression peaked 2 weeks after induction. |
T15 |
1647-1864 |
Sentence |
denotes |
In conclusion, the inducible R140Q-podocin mouse model is an auspicious model of the most common genetic cause of human nephrotic syndrome, with a spontaneous disease course strongly reminiscent of the human disorder. |
T16 |
1865-2089 |
Sentence |
denotes |
This model constitutes a valuable tool to test the efficacy of novel pharmacological interventions aimed to improve podocyte function and viability and attenuate proteinuria, glomerulosclerosis and progressive renal failure. |