ArticleHuman molecular genetics2016
Sensory and autonomic deficits in a new humanized mouse model of familial dysautonomia.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in familial dysautonomia.Molecular therapy. Nucleic acids · 2026Article
- Spinal hypermobility accelerates ossification in posterior longitudinal ligaments: insights from anFrontiers in physiology · 2025Article
- Genipin rescues developmental and degenerative defects in familial dysautonomia models and accelerates axon regeneration.Science translational medicine · 2024Article
- Article
- Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development.Cell stem cell · 2024Article
- Transcriptome analysis in a humanized mouse model of familial dysautonomia reveals tissue-specific gene expression disruption in the peripheral nervous system.Scientific reports · 2024Article
- Sensorimotor control in the congenital absence of functional muscle spindles.Experimental physiology · 2024Review
- Reduction of retinal ganglion cell death in mouse models of familial dysautonomia using AAV-mediated gene therapy and splicing modulators.Scientific reports · 2023Article
- Development of an oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia.American journal of human genetics · 2023Article
- Norepinephrine transporter defects lead to sympathetic hyperactivity in Familial Dysautonomia models.Nature communications · 2022Article
- Rescue of a familial dysautonomia mouse model by AAV9-Exon-specific U1 snRNA.American journal of human genetics · 2022Article
- Hypolacrimia and Alacrimia as Diagnostic Features for Genetic or Congenital Conditions.Investigative ophthalmology & visual science · 2022Review
- Loss of Elp1 disrupts trigeminal ganglion neurodevelopment in a model of familial dysautonomia.eLife · 2022Article
- Selective retinal ganglion cell loss and optic neuropathy in a humanized mouse model of familial dysautonomia.Human molecular genetics · 2022Article
- Elp1 is required for development of visceral sensory peripheral and central circuitry.Disease models & mechanisms · 2022Article
- Retrograde nerve growth factor signaling abnormalities and the pathogenesis of familial dysautonomia.Neural regeneration research · 2021Article
- Development of the Autonomic Nervous System: Clinical Implications.Seminars in neurology · 2020Review
- Induced pluripotent stem cells for disease modeling, cell therapy and drug discovery in genetic autonomic disorders: a review.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2019Review
- ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia.American journal of human genetics · 2019Article
- RNA Splicing and Disease: Animal Models to Therapies.Trends in genetics : TIG · 2019Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Familial dysautonomia (FD) is an autosomal recessive neurodegenerative disease that affects the development and survival of sensory and autonomic neurons. FD is caused by an mRNA splicing mutation in intron 20 of the IKBKAP gene that results in a tissue-specific skipping of exon 20 and a corresponding reduction of the inhibitor of kappaB kinase complex-associated protein (IKAP), also known as Elongator complex protein 1. To date, several promising therapeutic candidates for FD have been identified that target the underlying mRNA splicing defect, and increase functional IKAP protein. Despite these remarkable advances in drug discovery for FD, we lacked a phenotypic mouse model in which we could manipulate IKBKAP mRNA splicing to evaluate potential efficacy. We have, therefore, engineered a new mouse model that, for the first time, will permit to evaluate the phenotypic effects of splicing modulators and provide a crucial platform for preclinical testing of new therapies. This new mouse model, TgFD9; Ikbkap(Δ20/flox) was created by introducing the complete human IKBKAP transgene with the major FD splice mutation (TgFD9) into a mouse that expresses extremely low levels of endogenous Ikbkap (Ikbkap(Δ20/flox)). The TgFD9; Ikbkap(Δ20/flox) mouse recapitulates many phenotypic features of the human disease, including reduced growth rate, reduced number of fungiform papillae, spinal abnormalities, and sensory and sympathetic impairments, and recreates the same tissue-specific mis-splicing defect seen in FD patients. This is the first mouse model that can be used to evaluate in vivo the therapeutic effect of increasing IKAP levels by correcting the underlying FD splicing defect.
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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.