ArticleKidney international2014
A mouse Col4a4 mutation causing Alport glomerulosclerosis with abnormal collagen α3α4α5(IV) trimers.
Article in Kidney international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- A systematic review of kidney-on-a-chip-based models to study human renal (patho-)physiology.Disease models & mechanisms · 2023Pooled it
- Podocyte specific exon skipping after disease onset improves kidney pathology and function in a mouse model of Alport syndrome.Scientific reports · 2025Article
- Genotype-Based Molecular Mechanisms in Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2025Review
- The same heterozygousFrontiers in genetics · 2023Article
- A Comparative Presentation of Mouse Models That Recapitulate Most Features of Alport Syndrome.Genes · 2022Review
- Genetic Disorders of the Extracellular Matrix: From Cell and Gene Therapy to Future Applications in Regenerative Medicine.Annual review of genomics and human genetics · 2022Review
- COL4A4 variant recently identified: lessons learned in variant interpretation-a case report.BMC nephrology · 2022Article
- A novel model of nephrotic syndrome results from a point mutation in Lama5 and is modified by genetic background.Kidney international · 2022Article
- Molecular and Cellular Mechanisms Underlying the Initiation and Progression of Alport Glomerular Pathology.Frontiers in medicine · 2022Review
- Identification ofFrontiers in genetics · 2022Article
- Novel heterozygous mutation inFrontiers in genetics · 2022Article
- Creation of X-linked Alport syndrome rat model with Col4a5 deficiency.Scientific reports · 2021Article
- Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Alport Syndrome: A Primer for Clinicians.International journal of molecular sciences · 2021Review
- Uncovering Modifier Genes of X-Linked Alport Syndrome Using a Novel Multiparent Mouse Model.Journal of the American Society of Nephrology : JASN · 2021Article
- A glycine substitution in the collagenous domain of Col4a3 in mice recapitulates late onset Alport syndrome.Matrix biology plus · 2021Article
- Bidirectional, non-necrotizing glomerular crescents are the critical pathology in X-linked Alport syndrome mouse model harboring nonsense mutation of human COL4A5.Scientific reports · 2020Article
- A novel missense mutation ofTranslational pediatrics · 2020Article
- Using Genetic and Species Diversity to Tackle Kidney Disease.Trends in genetics : TIG · 2020Review
- Disease Modeling To Understand the Pathomechanisms of Human Genetic Kidney Disorders.Clinical journal of the American Society of Nephrology : CJASN · 2020Review
- Clinical trial recommendations for potential Alport syndrome therapies.Kidney international · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
A spontaneous mutation termed bilateral wasting kidneys (bwk) was identified in a colony of NONcNZO recombinant inbred mice. These mice exhibit a rapid increase of urinary albumin at an early age associated with glomerulosclerosis, interstitial nephritis, and tubular atrophy. The mutation was mapped to a location on chromosome 1 containing the Col4a3 and Col4a4 genes, for which mutations in the human orthologs cause the hereditary nephritis Alport syndrome. DNA sequencing identified a G-to-A mutation in the conserved GT splice donor of Col4a4 intron 30, resulting in skipping of exon 30 but maintaining the mRNA reading frame. Protein analyses showed that mutant collagen α3α4α5(IV) trimers were secreted and incorporated into the glomerular basement membrane (GBM), but levels were low, and GBM lesions typical of Alport syndrome were observed. Moving the mutation into the more renal damage-prone DBA/2J and 129S1/SvImJ backgrounds revealed differences in albuminuria and its rate of increase, suggesting an interaction between the Col4a4 mutation and modifier genes. This novel mouse model of Alport syndrome is the only one shown to accumulate abnormal collagen α3α4α5(IV) in the GBM, as also found in a subset of Alport patients. These mice will be valuable for testing potential therapies, for understanding abnormal collagen IV structure and assembly, and for gaining better insights into the mechanisms leading to Alport syndrome, and to the variability in the age of onset and associated phenotypes.
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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.