ArticleDevelopmental biology2015
A requirement for Gch1 and tetrahydrobiopterin in embryonic development.
Article in Developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BHOrphanet journal of rare diseases · 2020Guideline
- Inducible EndothelialHypertension (Dallas, Tex. : 1979) · 2026Article
- The Emerging Scenario of Ferroptosis in Pancreatic Cancer Tumorigenesis and Treatment.International journal of molecular sciences · 2024Review
- Ferroptosis in health and disease.Redox biology · 2024Review
- Tetrahydrobiopterin metabolism attenuates ROS generation and radiosensitivity through LDHA S-nitrosylation: novel insight into radiogenic lung injury.Experimental & molecular medicine · 2024Article
- Ferroptosis as an emerging target in sickle cell disease.Current research in toxicology · 2024Article
- BH4 supplementation reduces retinal cell death in ischaemic retinopathy.Scientific reports · 2023Article
- Adaptations of the 3T3-L1 adipocyte lipidome to defective ether lipid catabolism upon Agmo knockdown.Journal of lipid research · 2022Article
- GCH1 Deficiency Activates Brain Innate Immune Response and Impairs Tyrosine Hydroxylase Homeostasis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Ninety-six-hour starved peripheral blood mononuclear cell supernatant inhibited LA7 breast cancer stem cells induced tumorFrontiers in immunology · 2022Article
- Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines.Nature communications · 2021Article
- Ferroptosis: mechanisms, biology and role in disease.Nature reviews. Molecular cell biology · 2021Review
- When the genome bluffs: a tandem duplication event during generation of a novel Agmo knockout mouse model fools routine genotyping.Cell & bioscience · 2021Article
- The Emerging Physiological Role of AGMO 10 Years after Its Gene Identification.Life (Basel, Switzerland) · 2021Review
- Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes Mellitus in Mice.Journal of the American Heart Association · 2018Article
- Pregnancy management and outcome in patients with four different tetrahydrobiopterin disorders.Journal of inherited metabolic disease · 2018Article
- Roles for endothelial cell and macrophage Gch1 and tetrahydrobiopterin in atherosclerosis progression.Cardiovascular research · 2018Article
- Combining Human and Rodent Genetics to Identify New Analgesics.Neuroscience bulletin · 2018Review
- Development, characterization and comparisons of targeted and non-targeted metabolomics methods.PloS one · 2018Article
- Update on the Genetics of Dystonia.Current neurology and neuroscience reports · 2017Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
introductionGTP cyclohydrolase I (GTPCH) catalyses the first and rate-limiting reaction in the synthesis of the enzymatic cofactor, tetrahydrobiopterin (BH4). Loss of function mutations in the GCH1 gene lead to congenital neurological diseases such as DOPA-responsive dystonia and hyperphenylalaninemia. However, little is known about how GTPCH and BH4 affects embryonic development in utero, and in particular whether metabolic replacement or supplementation in pregnancy is sufficient to rescue genetic GTPCH deficiency in the developing embryo. METHODS AND
resultsGch1 deficient mice were generated by the insertion of loxP sites flanking exons 2-3 of the Gch1 gene. Gch1(fl/fl) mice were bred with Sox2cre mice to generate mice with global Gch1 deficiency. Genetic ablation of Gch1 caused embryonic lethality by E13.5. Despite loss of Gch1 mRNA and GTPCH enzymatic activity, whole embryo BH4 levels were maintained until E11.5, indicating sufficient maternal transfer of BH4 to reach this stage of development. After E11.5, Gch1(-/-) embryos were deficient in BH4, but an unbiased metabolomic screen indicated that the lethality was not due to a gross disturbance in metabolic profile. Embryonic lethality in Gch1(-/-) embryos was not caused by structural abnormalities, but was associated with significant bradycardia at E11.5. Embryonic lethality was not rescued by maternal supplementation of BH4, but was partially rescued, up to E15.5, by maternal supplementation of BH4 and l-DOPA.
conclusionThese findings demonstrate a requirement for Gch1 in embryonic development and have important implications for the understanding of pathogenesis and treatment of genetic BH4 deficiencies, as well as the identification of new potential roles for BH4.
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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.