ArticleHuman molecular genetics2011
A valid mouse model of AGRIN-associated congenital myasthenic syndrome.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 42 citations in OpenAlex.
- Muscle-Specific Kinase Signaling and Its Therapeutic Potential.Muscle & nerve · 2026Review
- Congenital Myasthenic Syndrome in Doberman Pinscher Dogs Is Associated with a Homozygous Missense Variant inBiomolecules · 2026Article
- Gene-specific response to muscle specific kinase agonist antibody in the treatment of congenital myasthenic syndromes.Brain communications · 2026Article
- Galactose treatment rescues neuromuscular junction transmission in glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) deficient mice.Human molecular genetics · 2025Article
- A conserved RNA switch for acetylcholine receptor clustering at neuromuscular junctions in chordates.bioRxiv : the preprint server for biology · 2024Article
- GDP-Mannose Pyrophosphorylase B (Genes · 2023Review
- Urinary protein biomarkers based on LC-MS/MS analysis to discriminate vascular dementia from Alzheimer's disease in Han Chinese population.Frontiers in aging neuroscience · 2023Article
- The Impact of Mitochondrial Deficiencies in Neuromuscular Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Congenital myasthenic syndrome-associated agrin variants affect clustering of acetylcholine receptors in a domain-specific manner.JCI insight · 2020Article
- The Neuromuscular Junction in Health and Disease: Molecular Mechanisms Governing Synaptic Formation and Homeostasis.Frontiers in molecular neuroscience · 2020Review
- Modulation of the Acetylcholine Receptor Clustering Pathway Improves Neuromuscular Junction Structure and Muscle Strength in a Mouse Model of Congenital Myasthenic Syndrome.Frontiers in molecular neuroscience · 2020Article
- A mechanism in agrin signaling revealed by a prevalent Rapsyn mutation in congenital myasthenic syndrome.eLife · 2019Article
- Article
- A homozygous mutation in GMPPB leads to centronuclear myopathy with combined pre- and postsynaptic defects of neuromuscular transmission.Neuromuscular disorders : NMD · 2019Article
- Model validity for preclinical studies in precision medicine: precisely how precise do we need to be?Mammalian genome : official journal of the International Mammalian Genome Society · 2019Article
- GFPT1 deficiency in muscle leads to myasthenia and myopathy in mice.Human molecular genetics · 2018Article
- Muscle-Specific Tyrosine Kinase and Myasthenia Gravis Owing to Other Antibodies.Neurologic clinics · 2018Review
- Animal Models of the Neuromuscular Junction, Vitally Informative for Understanding Function and the Molecular Mechanisms of Congenital Myasthenic Syndromes.International journal of molecular sciences · 2018Review
- Novel SEA and LG2 Agrin mutations causing congenital Myasthenic syndrome.Orphanet journal of rare diseases · 2017Article
- A Novel Egr-1-Agrin Pathway and Potential Implications for Regulation of Synaptic Physiology and Homeostasis at the Neuromuscular Junction.Frontiers in aging neuroscience · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Congenital myasthenic syndromes (CMS) are inherited diseases affecting the neuromuscular junction (NMJ). Mutations in AGRIN (AGRN) and other genes in the AGRIN signaling pathway cause CMS, and gene targeting studies in mice confirm the importance of this pathway for NMJ formation. However, these mouse mutations are complete loss-of-function alleles that result in an embryonic failure of NMJ formation, and homozygous mice do not survive postpartum. Therefore, mouse models of AGRIN-related CMS that would allow preclinical testing or studies of postnatal disease progression are lacking. Using chemical mutagenesis in mice, we identified a point mutation in Agrn that results in a partial loss-of-function allele, creating a valid model of CMS. The mutation changes phenylalanine 1061 to serine in the SEA domain of AGRIN, a poorly characterized motif shared by other extracellular proteoglycans. NMJs in homozygous mice progressively degrade postnataly. Severity differs with genetic background, in different muscles, and in different regions within a muscle in a pattern matching mouse models of motor neuron disease. Mutant NMJs have decreased acetylcholine receptor density and an increased subsynaptic reticulum, evident by electron microscopy. Synapses eventually denervate and the muscles atrophy. Molecularly, several factors contribute to the partial loss of AGRIN's function. The mutant protein is found at NMJs, but is processed differently than wild-type, with decreased glycosylation, changes in sensitivity to the protease neurotrypsin and other proteolysis, and less efficient externalization and secretion. Therefore, the Agrn point mutation is a model for CMS caused by Agrn mutations and potentially other related neuromuscular diseases.
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.