ArticlePLoS genetics2014
A dominant-negative mutation of mouse Lmx1b causes glaucoma and is semi-lethal via LDB1-mediated dimerization [corrected].
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.Nature communications · 2018Pooled it
- Proteasome inhibition alleviates proteinuria in Lmx1b knock-in mice with dysfunctional LIM domains.Nature communications · 2026Article
- Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Intraocular pressure induced blood retinal barrier compromise in mouse models and human glaucoma.Nature communications · 2026Article
- Chromatin dynamics identifies 78 genes at loci associated with elevated intraocular pressure and primary open-angle glaucoma.bioRxiv : the preprint server for biology · 2026Article
- Article
- Characterisation of lmx1b paralogues in zebrafish reveals divergent roles in skeletal, kidney and muscle development.Biology open · 2025Article
- Single-cell profiling of trabecular meshwork identifies mitochondrial dysfunction in a glaucoma model that is protected by vitamin B3 treatment.bioRxiv : the preprint server for biology · 2025Article
- Proliferative retinopathy in nail-patella syndrome.American journal of ophthalmology case reports · 2025Article
- Pyruvate and related energetic metabolites modulate resilience against high genetic risk for glaucoma.eLife · 2025Article
- Pyruvate and Related Energetic Metabolites Modulate Resilience Against High Genetic Risk for Glaucoma.bioRxiv : the preprint server for biology · 2025Article
- Structural framework to address variant-gene relationship in primary open-angle glaucoma.Vision research · 2025Review
- MicroRNAs as biomarkers in glaucoma and potential therapeutic targets.Neural regeneration research · 2022Review
- Transcription Factor Lmx1b Negatively Regulates Osteoblast Differentiation and Bone Formation.International journal of molecular sciences · 2022Article
- Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.Investigative ophthalmology & visual science · 2022Review
- Deletion of transcription factor AP-2β from the developing murine trabecular meshwork region leads to progressive glaucomatous changes.Journal of neuroscience research · 2022Article
- MicroRNAs in the aqueous humor of patients with different types of glaucoma.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2021Article
- Article
- Review
- Genetic background modifies vulnerability to glaucoma-related phenotypes inDisease models & mechanisms · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
Mutations in the LIM-homeodomain transcription factor LMX1B cause nail-patella syndrome, an autosomal dominant pleiotrophic human disorder in which nail, patella and elbow dysplasia is associated with other skeletal abnormalities and variably nephropathy and glaucoma. It is thought to be a haploinsufficient disorder. Studies in the mouse have shown that during development Lmx1b controls limb dorsal-ventral patterning and is also required for kidney and eye development, midbrain-hindbrain boundary establishment and the specification of specific neuronal subtypes. Mice completely deficient for Lmx1b die at birth. In contrast to the situation in humans, heterozygous null mice do not have a mutant phenotype. Here we report a novel mouse mutant Icst, an N-ethyl-N-nitrosourea-induced missense substitution, V265D, in the homeodomain of LMX1B that abolishes DNA binding and thereby the ability to transactivate other genes. Although the homozygous phenotypic consequences of Icst and the null allele of Lmx1b are the same, heterozygous Icst elicits a phenotype whilst the null allele does not. Heterozygous Icst causes glaucomatous eye defects and is semi-lethal, probably due to kidney failure. We show that the null phenotype is rescued more effectively by an Lmx1b transgene than is Icst. Co-immunoprecipitation experiments show that both wild-type and Icst LMX1B are found in complexes with LIM domain binding protein 1 (LDB1), resulting in lower levels of functional LMX1B in Icst heterozygotes than null heterozygotes. We conclude that Icst is a dominant-negative allele of Lmx1b. These findings indicate a reassessment of whether nail-patella syndrome is always haploinsufficient. Furthermore, Icst is a rare example of a model of human glaucoma caused by mutation of the same gene in humans and mice.
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