ArticleHuman molecular genetics2010
A humanized Smn gene containing the SMN2 nucleotide alteration in exon 7 mimics SMN2 splicing and the SMA disease phenotype.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 31 citations in OpenAlex.
- Dysregulation of innate immune signaling in animal models of spinal muscular atrophy.BMC biology · 2024Article
- Exon Skipping Through Chimeric AntisenseNucleic acid therapeutics · 2022Article
- Motor transmission defects with sex differences in a new mouse model of mild spinal muscular atrophy.EBioMedicine · 2020Article
- Comprehensive Modeling of Spinal Muscular Atrophy inFrontiers in molecular neuroscience · 2019Article
- RNA Splicing and Disease: Animal Models to Therapies.Trends in genetics : TIG · 2019Review
- Modeling the ferrochelatase c.315-48C modifier mutation for erythropoietic protoporphyria (EPP) in mice.Disease models & mechanisms · 2017Article
- Species-dependent splice recognition of a cryptic exon resulting from a recurrent intronic CEP290 mutation that causes congenital blindness.International journal of molecular sciences · 2015Article
- Absence of an intron splicing silencer in porcine Smn1 intron 7 confers immunity to the exon skipping mutation in human SMN2.PloS one · 2014Article
- Neurotransmitter release in motor nerve terminals of a mouse model of mild spinal muscular atrophy.Journal of anatomy · 2014Article
- Spinal muscular atrophy: an update on therapeutic progress.Biochimica et biophysica acta · 2013Review
- Unexpected CEP290 mRNA splicing in a humanized knock-in mouse model for Leber congenital amaurosis.PloS one · 2013Article
- Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model.Human molecular genetics · 2012Article
- Mouse models of SMA: tools for disease characterization and therapeutic development.Human genetics · 2012Review
- New therapeutic approaches to spinal muscular atrophy.Current neurology and neuroscience reports · 2012Review
- Identification of a Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitor, BIP-135, that Prolongs the Median Survival Time of Δ7 SMA KO Mouse Model of Spinal Muscular Atrophy.ACS chemical neuroscience · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Proximal spinal muscular atrophy (SMA) is a neurodegenerative disease caused by low levels of the survival motor neuron (SMN) protein. In humans, SMN1 and SMN2 encode the SMN protein. In SMA patients, the SMN1 gene is lost and the remaining SMN2 gene only partially compensates. Mediated by a C>T nucleotide transition in SMN2, the inefficient recognition of exon 7 by the splicing machinery results in low levels of SMN. Because the SMN2 gene is capable of expressing SMN protein, correction of SMN2 splicing is an attractive therapeutic option. Although current mouse models of SMA characterized by Smn knock-out alleles in combination with SMN2 transgenes adequately model the disease phenotype, their complex genetics and short lifespan have hindered the development and testing of therapies aimed at SMN2 splicing correction. Here we show that the mouse and human minigenes are regulated similarly by conserved elements within in exon 7 and its downstream intron. Importantly, the C>T mutation is sufficient to induce exon 7 skipping in the mouse minigene as in the human SMN2. When the mouse Smn gene was humanized to carry the C>T mutation, keeping it under the control of the endogenous promoter, and in the natural genomic context, the resulting mice exhibit exon 7 skipping and mild adult onset SMA characterized by muscle weakness, decreased activity and an alteration of the muscle fibers size. This Smn C>T mouse represents a new model for an adult onset form of SMA (type III/IV) also know as the Kugelberg-Welander disease.
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.