PubMed:29049388 JSONTXT 23 Projects

Annnotations TAB TSV DIC JSON TextAE

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.