ArticleDisease models & mechanisms2021
Recessive, gain-of-function toxicity in an APOL1 BAC transgenic mouse model mirrors human APOL1 kidney disease.
Article in Disease models & mechanisms, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- Coding, modifier, and regulatory effects shape circulating APOL1 levels.Human molecular genetics · 2026Article
- APOL1 risk alleles modulate T cell receptor signaling to promote allograft rejection.The Journal of clinical investigation · 2026Article
- Germline-targeted baboon apolipoprotein L-1 protects mice against African trypanosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- APOL1 plasma membrane pools resist rapid protein degradation.Scientific reports · 2026Article
- The role of suPAR and related proteins in kidney, heart diseases, and diabetes.The Journal of clinical investigation · 2026Review
- APOL1 G1 and G2 risk alleles modulate severity of diet-induced obesity in a transgenic mouse model.bioRxiv : the preprint server for biology · 2025Article
- APOL1-mediated kidney disease: a narrative review of the lessons learnt from the past 15 years.BMC nephrology · 2025Review
- A novelRenal failure · 2025Article
- APOL1 kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.Kidney international · 2025Article
- Review
- Article
- HIV-1 Nef synergizes with APOL1-G1 to induce nephrocyte cell death in HIV-related kidney diseases.Disease models & mechanisms · 2025Article
- Review
- G1 and G2 ApolipoproteinL1 modulate macrophage inflammation and lipid accumulation through the polyamine pathway.bioRxiv : the preprint server for biology · 2025Article
- Multiethnic prevalence of theClinical kidney journal · 2025Article
- Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.Nature communications · 2025Article
- Pathogenesis of HIV-associated nephropathy in children and adolescents: taking a hard look 40 years later in the era of gene-environment interactions.American journal of physiology. Renal physiology · 2024Review
- Differing sensitivities to angiotensin converting enzyme inhibition of kidney disease mediated by APOL1 high-risk variants G1 and G2.Kidney international · 2024Article
- INF2 mutations cause kidney disease through a gain-of-function mechanism.Science advances · 2024Article
- Protein-truncating variant in APOL3 increases chronic kidney disease risk in epistasis with APOL1 risk alleles.JCI insight · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
People of recent sub-Saharan African ancestry develop kidney failure much more frequently than other groups. A large fraction of this disparity is due to two coding sequence variants in the APOL1 gene. Inheriting two copies of these APOL1 risk variants, known as G1 and G2, causes high rates of focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy and hypertension-associated end-stage kidney disease. Disease risk follows a recessive mode of inheritance, which is puzzling given the considerable data that G1 and G2 are toxic gain-of-function variants. We developed coisogenic bacterial artificial chromosome (BAC) transgenic mice harboring either the wild-type (G0), G1 or G2 forms of human APOL1. Expression of interferon gamma (IFN-γ) via plasmid tail vein injection results in upregulation of APOL1 protein levels together with robust induction of heavy proteinuria and glomerulosclerosis in G1/G1 and G2/G2 but not G0/G0 mice. The disease phenotype was greater in G2/G2 mice. Neither heterozygous (G1/G0 or G2/G0) risk variant mice nor hemizygous (G1/-, G2/-) mice had significant kidney injury in response to IFN-γ, although the heterozygous mice had a greater proteinuric response than the hemizygous mice, suggesting that the lack of significant disease in humans heterozygous for G1 or G2 is not due to G0 rescue of G1 or G2 toxicity. Studies using additional mice (multicopy G2 and a non-isogenic G0 mouse) supported the notion that disease is largely a function of the level of risk variant APOL1 expression. Together, these findings shed light on the recessive nature of APOL1-nephropathy and present an important model for future studies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.