作者
Aude Dorison, Irene Ghobrial, Alison Graham, Thanushi Peiris, Thomas A Forbes, Michael See, Mithun Das, Moin A Saleem, Catherine Quinlan, Kynan T Lawlor, Mirana Ramialison, Sara E Howden, Melissa H Little
发表日期
2023/1/1
期刊
Journal of the American Society of Nephrology
卷号
34
期号
1
页码范围
88-109
出版商
LWW
简介
Background
NPHS2 variants are the most common cause of steroid-resistant nephrotic syndrome in children> 1 month old. Missense NPHS2 variants were reported to cause mistrafficking of the encoded protein, PODOCIN, but this conclusion was on the basis of overexpression in some nonpodocyte cell lines.
Methods
We generated a series of human induced pluripotent stem cell (iPSC) lines bearing pathogenic missense variants of NPHS2, encoding the protein changes p. G92C, p. P118L, p. R138Q, p. R168H, and p. R291W, and control lines. iPSC lines were also generated from a patient with steroid-resistant nephrotic syndrome (p. R168H homozygote) and a healthy heterozygous parent. All lines were differentiated into kidney organoids. Immunofluorescence assessed PODOCIN expression and subcellular localization. Podocytes were transcriptionally profiled and PODOCIN-NEPHRIN interaction interrogated …
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A Dorison, I Ghobrial, A Graham, T Peiris, TA Forbes… - Journal of the American Society of Nephrology, 2023
