ArticleCell reports2018
Genomic Knockout of Two Presumed Forelimb Tbx5 Enhancers Reveals They Are Nonessential for Limb Development.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- Experience with patients presenting with the clinical features of Holt-Oram syndrome: a single center retrospective study.Journal of cardiothoracic surgery · 2026Article
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Genetic knockout suggests Isl1 enhancer redundancy in mouse hindlimb development.Developmental biology · 2025Article
- Exploring the roles of conserved context-dependent cis-regulatory elements (cdCREs) in multicellularity, human health and disease.The FEBS journal · 2025Review
- Early retinoic acid signaling organizes the body axis and defines domains for the forelimb and eye.Current topics in developmental biology · 2025Review
- Sexually dimorphic renal expression of mouse Klotho is directed by a kidney-specific distal enhancer responsive to HNF1b.Communications biology · 2024Article
- Sall genes regulate hindlimb initiation in mouse embryos.Genetics · 2024Article
- Sexually dimorphic renal expression ofResearch square · 2024Article
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- Lateral thinking in syndromic congenital cardiovascular disease.Disease models & mechanisms · 2023Article
- Noncoding Mutations in a Thyroid Hormone Receptor Gene That Impair Cone Photoreceptor Function.Endocrinology · 2023Article
- Evolutionary genetics of flipper forelimb and hindlimb loss from limb development-related genes in cetaceans.BMC genomics · 2022Article
- Article
- Context-dependant enhancers as a reservoir of functional polymorphisms and epigenetic markers linked to alcohol use disorders and comorbidities.Addiction neuroscience · 2022Review
- Review
- Tbx5 driveseLife · 2021Article
- Limb positioning and initiation: An evolutionary context of pattern and formation.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Review
- Functional in vivo characterization of sox10 enhancers in neural crest and melanoma development.Communications biology · 2021Article
- Enhancer redundancy in development and disease.Nature reviews. Genetics · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
A standard approach in the identification of transcriptional enhancers is the use of transgenic animals carrying DNA elements joined to reporter genes inserted randomly in the genome. We examined elements near Tbx5, a gene required for forelimb development in humans and other vertebrates. Previous transgenic studies reported a mammalian Tbx5 forelimb enhancer located in intron 2 containing a putative retinoic acid response element and a zebrafish tbx5a forelimb (pectoral fin) enhancer located downstream that is conserved from fish to mammals. We used CRISPR/Cas9 gene editing to knockout the endogenous elements and unexpectedly found that deletion of the intron 2 and downstream elements, either singly or together in double knockouts, resulted in no effect on forelimb development. Our findings show that reporter transgenes may not identify endogenous enhancers and that in vivo genetic loss-of-function studies are required, such as CRISPR/Cas9, which is similar in effort to production of animals carrying reporter transgenes.
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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.