ArticleJCI insight2019
Precocious chondrocyte differentiation disrupts skeletal growth in Kabuki syndrome mice.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- In utero rescue of neurological dysfunction in a mouse model of Wiedemann-Steiner syndrome.JCI insight · 2025Article
- In utero rescue of neurological dysfunction in a mouse model of Wiedemann-Steiner syndrome.JCI insight · 2025Article
- Deficiency of KMT2D causes autistic-like behavior in mice and zebrafish.Communications biology · 2025Article
- Behavioural impairments in a mouse model of Kabuki syndrome associated with dopaminergic and neuroinflammatory modulations.Acta neuropsychiatrica · 2025Article
- MLL4 regulates postnatal palate growth and midpalatal suture development.Frontiers in cell and developmental biology · 2025Article
- MLL4 regulates postnatal palate growth and midpalatal suture development.bioRxiv : the preprint server for biology · 2024Article
- Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.Genome research · 2024Article
- Growth deficiency in a mouse model of Kabuki syndrome 2 bears mechanistic similarities to Kabuki syndrome 1.PLoS genetics · 2024Article
- Growth deficiency in a mouse model of Kabuki syndrome 2 bears mechanistic similarities to Kabuki syndrome 1.PLoS genetics · 2024Article
- Role of histone methyltransferase KMT2D in BMSC osteogenesis via AKT signaling.Regenerative therapy · 2024Article
- Five years of experience in the Epigenetics and Chromatin Clinic: what have we learned and where do we go from here?Human genetics · 2024Article
- Knockdown of Kmt2d leads to growth impairment by activating the Akt/β-catenin signaling pathway.G3 (Bethesda, Md.) · 2024Article
- A mouse model of Weaver syndrome displays overgrowth and excess osteogenesis reversible with KDM6A/6B inhibition.JCI insight · 2024Article
- A mouse model of Weaver syndrome displays overgrowth and excess osteogenesis reversible with KDM6A/6B inhibition.JCI insight · 2024Article
- Growth disorders caused by variants in epigenetic regulators: progress and prospects.Frontiers in endocrinology · 2024Review
- Article
- SETting up the genome: KMT2D and KDM6A genomic function in the Kabuki syndrome craniofacial developmental disorder.Birth defects research · 2023Review
- Article
- Temporal transcriptome features identify early skeletal commitment during human epiphysis development at single-cell resolution.iScience · 2023Article
- Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Kabuki syndrome 1 (KS1) is a Mendelian disorder of the epigenetic machinery caused by mutations in the gene encoding KMT2D, which methylates lysine 4 on histone H3 (H3K4). KS1 is characterized by intellectual disability, postnatal growth retardation, and distinct craniofacial dysmorphisms. A mouse model (Kmt2d+/βGeo) exhibits features of the human disorder and has provided insight into other phenotypes; however, the mechanistic basis of skeletal abnormalities and growth retardation remains elusive. Using high-resolution micro-CT, we show that Kmt2d+/βGeo mice have shortened long bones and ventral bowing of skulls. In vivo expansion of growth plates within skulls and long bones suggests disrupted endochondral ossification as a common disease mechanism. Stable chondrocyte cell lines harboring inactivating mutations in Kmt2d exhibit precocious differentiation, further supporting this mechanism. A known inducer of chondrogenesis, SOX9, and its targets show markedly increased expression in Kmt2d-/- chondrocytes. By transcriptome profiling, we identify Shox2 as a putative KMT2D target. We propose that decreased KMT2D-mediated H3K4me3 at Shox2 releases Sox9 inhibition and thereby leads to enhanced chondrogenesis, providing a potentially novel and plausible explanation for precocious chondrocyte differentiation. Our findings provide insight into the pathogenesis of growth retardation in KS1 and suggest therapeutic approaches for this and related disorders.
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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.