GEO series

Renal Proximal Tubule Cell-specific Megalin Deletion Induces Tubulointerstitial Nephritis in Mice Fed Western Diet

GSE268879 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2024/07/04 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 24 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 24 samples: 6 × WT_WD2 vs 6 × KO_WD2 vs 6 × WT_WD12 vs 6 × KO_WD12Groups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western DietArteriosclerosis, thrombosis, and vascular biology · 2025

Summary (written by the submitters)

Pharmacological inhibition of megalin (also known as low-density lipoprotein receptor-related protein 2: LRP2) attenuates atherosclerosis in hypercholesterolemic mice. Since megalin is abundant in renal proximal tubule cells (PTCs), PTC-LRP2 +/+ and -/- littermates in an LDL receptor -/- background were generated and fed a Western diet to determine effects of PTC-derived megalin on atherosclerosis.

Read the full summary ↓

PTC-specific megalin deletion did not attenuate atherosclerosis in LDL receptor -/- mice in either sex. Serendipitously, we discovered that PTC-specific megalin deletion led to interstitial infiltration of CD68+ cells and tubular atrophy. The pathology was only evident in male PTC-LRP2 -/- mice fed the Western diet, but not in mice fed a normal laboratory diet. Renal pathologies were also observed in male PTC-LRP2 -/- mice in an LDL receptor +/+ background fed the same Western diet, demonstrating that the renal pathologies were dependent on diet and not hypercholesterolemia. By contrast, female PTC-LRP2 -/- mice had no apparent renal pathologies. In vivo multiphoton microscopy demonstrated that PTC-specific megalin deletion dramatically diminished albumin accumulation in PTCs within 10 days of Western diet feeding. RNA sequencing analyses demonstrated the upregulation of inflammation-related pathways in kidney. Overall, PTC-specific megalin deletion leads to tubulointerstitial nephritis in mice fed Western diet, with severe pathologies in male mice.

Published in

Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western Diet

Amioka N, Franklin MK, Kukida M et al. · Arteriosclerosis, thrombosis, and vascular biology 2025 · PMID 39569521 · doi:10.1161/ATVBAHA.124.321366

This dataset

Open GSE268879 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE268879_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1119377 and SRA study SRP511308. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39569521) ↗

Study design

6 × WT_WD2 vs 6 × KO_WD2 vs 6 × WT_WD12 vs 6 × KO_WD12

Supports a between-group comparison across 24 samples.

How we read this: 4 replicated groups read from 24 sample titles; they account for 24 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8301968 WT_WD2_1 WT_WD2
GSM8301969 KO_WD2_1 KO_WD2
GSM8301970 WT_WD2_2 WT_WD2
GSM8301971 KO_WD2_2 KO_WD2
GSM8301972 WT_WD2_3 WT_WD2
GSM8301973 KO_WD2_3 KO_WD2
GSM8301974 KO_WD2_4 KO_WD2
GSM8301975 KO_WD2_5 KO_WD2
GSM8301976 WT_WD2_4 WT_WD2
GSM8301977 WT_WD2_5 WT_WD2
GSM8301978 WT_WD2_6 WT_WD2
GSM8301979 KO_WD2_6 KO_WD2
GSM8301980 WT_WD12_1 WT_WD12
GSM8301981 KO_WD12_1 KO_WD12
GSM8301982 KO_WD12_2 KO_WD12
GSM8301983 WT_WD12_2 WT_WD12
GSM8301984 KO_WD12_3 KO_WD12
GSM8301985 KO_WD12_4 KO_WD12
GSM8301986 KO_WD12_5 KO_WD12
GSM8301987 KO_WD12_6 KO_WD12
GSM8301988 WT_WD12_3 WT_WD12
GSM8301989 WT_WD12_4 WT_WD12
GSM8301990 WT_WD12_5 WT_WD12
GSM8301991 WT_WD12_6 WT_WD12

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