ArticleThe Journal of clinical investigation2023
A murine model of hnRNPH2-related neurodevelopmental disorder reveals a mechanism for genetic compensation by Hnrnph1.
Article in The Journal of clinical investigation, 2023. 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 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Proteomic profile of hippocampal growth cones through early postnatal development.Development (Cambridge, England) · 2026Article
- Conditional Modeling of GNAO1 Disorder Dissociates Circuit Specific Contributions to Pathology and Rationalizes Ameliorative Strategies.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- RNArchitects: how hnRNPs shape neuronal landscapes.Brain : a journal of neurology · 2026Review
- Preclinical evaluation of antisense oligonucleotide therapy in a mouse model ofbioRxiv : the preprint server for biology · 2025Article
- Compensation for X-linked Pdha1 silencing by Pdha2 is essential for meiotic double-strand break repair in spermatogenesis.Development (Cambridge, England) · 2025Article
- Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring.Scientific reports · 2025Article
- Exploratory analysis of a Novel RACK1 mutation and its potential role in epileptic seizures via Microglia activation.Journal of neuroinflammation · 2025Article
- RNA granules in flux: dynamics to balance physiology and pathology.Nature reviews. Neuroscience · 2024Review
- hnRNPs: roles in neurodevelopment and implication for brain disorders.Frontiers in molecular neuroscience · 2024Review
- hnRNPH2 gain-of-function mutations reveal therapeutic strategies and a role for RNA granules in neurodevelopmental disorders.The Journal of clinical investigation · 2023Article
Corrections and comments
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- Erratum issued
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations in HNRNPH2 cause an X-linked neurodevelopmental disorder with features that include developmental delay, motor function deficits, and seizures. More than 90% of patients with hnRNPH2 have a missense mutation within or adjacent to the nuclear localization signal (NLS) of hnRNPH2. Here, we report that hnRNPH2 NLS mutations caused reduced interaction with the nuclear transport receptor Kapβ2 and resulted in modest cytoplasmic accumulation of hnRNPH2. We generated 2 knockin mouse models with human-equivalent mutations in Hnrnph2 as well as Hnrnph2-KO mice. Knockin mice recapitulated clinical features of the human disorder, including reduced survival in male mice, impaired motor and cognitive functions, and increased susceptibility to audiogenic seizures. In contrast, 2 independent lines of Hnrnph2-KO mice showed no detectable phenotypes. Notably, KO mice had upregulated expression of Hnrnph1, a paralog of Hnrnph2, whereas knockin mice failed to upregulate Hnrnph1. Thus, genetic compensation by Hnrnph1 may counteract the loss of hnRNPH2. These findings suggest that HNRNPH2-related disorder may be driven by a toxic gain of function or a complex loss of HNRNPH2 function with impaired compensation by HNRNPH1. The knockin mice described here are an important resource for preclinical studies to assess the therapeutic benefit of gene replacement or knockdown of mutant hnRNPH2.
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Registered trials
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