ArticleThe Journal of clinical investigation2005
An inversion involving the mouse Shh locus results in brachydactyly through dysregulation of Shh expression.
Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 75 citations in OpenAlex.
- A misplaced lncRNA causes brachydactyly in humans.The Journal of clinical investigation · 2012Trial
- Pathogenesis and potential therapeutic targets of trichorhinophalangeal syndrome; lessons obtained from animal studies.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Review
- Brachydactyly with Novel BMP8A and FGFR1 Variants: A Case Report with Review of Literature.Advanced genetics (Hoboken, N.J.) · 2025Article
- Suppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1.Nature communications · 2024Article
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- A single-cell transcriptome atlas profiles early organogenesis in human embryos.Nature cell biology · 2023Article
- Article
- Review
- A Novel NonsenseFrontiers in genetics · 2020Article
- Mechanisms of synovial joint and articular cartilage development.Cellular and molecular life sciences : CMLS · 2019Review
- Joints in the appendicular skeleton: Developmental mechanisms and evolutionary influences.Current topics in developmental biology · 2019Review
- Structural variation in the 3D genome.Nature reviews. Genetics · 2018Review
- Enhancer adoption caused by genomic insertion elicits interdigitalProceedings of the National Academy of Sciences of the United States of America · 2018Article
- The Shh Topological Domain Facilitates the Action of Remote Enhancers by Reducing the Effects of Genomic Distances.Developmental cell · 2016Article
- Article
- Mapping the Shh long-range regulatory domain.Development (Cambridge, England) · 2014Article
- Genesis and morphogenesis of limb synovial joints and articular cartilage.Matrix biology : journal of the International Society for Matrix Biology · 2014Review
- Disruption of long-range gene regulation in human genetic disease: a kaleidoscope of general principles, diverse mechanisms and unique phenotypic consequences.Human genetics · 2014Review
- Functional and topological characteristics of mammalian regulatory domains.Genome research · 2014Article
- Targeted disruption of Hotair leads to homeotic transformation and gene derepression.Cell reports · 2013Article
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13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Short digits (Dsh) is a radiation-induced mouse mutant. Homozygous mice are characterized by multiple defects strongly resembling those resulting from Sonic hedgehog (Shh) inactivation. Heterozygous mice show a limb reduction phenotype with fusion and shortening of the proximal and middle phalanges in all digits, similar to human brachydactyly type A1, a condition caused by mutations in Indian hedgehog (IHH). We mapped Dsh to chromosome 5 in a region containing Shh and were able to demonstrate an inversion comprising 11.7 Mb. The distal breakpoint is 13.298 kb upstream of Shh, separating the coding sequence from several putative regulatory elements identified by interspecies comparison. The inversion results in almost complete downregulation of Shh expression during E9.5-E12.5, explaining the homozygous phenotype. At E13.5 and E14.5, however, Shh is upregulated in the phalangeal anlagen of Dsh/+ mice, at a time point and in a region where WT Shh is never expressed. The dysregulation of Shh expression causes the local upregulation of hedgehog target genes such as Gli1-3, patched, and Pthlh, as well as the downregulation of Ihh and Gdf5. This results in shortening of the digits through an arrest of chondrocyte differentiation and the disruption of joint development.
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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.