ArticleGenes & development2008
VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5.
Article in Genes & development, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 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.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Application of microRNA in Human Osteoporosis and Fragility Fracture: A Systemic Review of Literatures.International journal of molecular sciences · 2021Pooled it
- PCSK5 promotes angiogenesis and cardiac repair after myocardial infarction.Nature communications · 2026Article
- Structural and functional brain asymmetry in relation to heterogeneous causes of situs inversus totalis.Brain structure & function · 2026Article
- Simplifying causal gene identification in GWAS loci.PLoS genetics · 2026Article
- Ventral body wall closure: Mechanistic insights from mouse models and translation to human pathology.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Review
- Embryonic Lethal Phenotyping to Identify Candidate Genes Related with Birth Defects.International journal of molecular sciences · 2024Article
- Molecular Pathways and Animal Models of Truncus Arteriosus.Advances in experimental medicine and biology · 2024Review
- Molecular Pathways and Animal Models of d-Transposition of the Great Arteries.Advances in experimental medicine and biology · 2024Review
- hPSC-derived sacral neural crest enables rescue in a severe model of Hirschsprung's disease.Cell stem cell · 2023Article
- Gastrulation and Body Axes Formation: A Molecular Concept and Its Clinical Correlates.The Malaysian journal of medical sciences : MJMS · 2022Review
- The transcriptomic landscape of caudal cell mass in different developmental stages of the chick embryo.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Article
- Exome sequencing identifies variants in infants with sacral agenesis.Birth defects research · 2022Article
- Breaking constraint of mammalian axial formulae.Nature communications · 2022Article
- Bioinformatics network analyses of growth differentiation factor 11.Open life sciences · 2022Article
- Mouse embryo phenotyping using X-ray microCT.Frontiers in cell and developmental biology · 2022Review
- Heritability and De Novo Mutations in Oesophageal Atresia and Tracheoesophageal Fistula Aetiology.Genes · 2021Review
- Developmental basis of trachea-esophageal birth defects.Developmental biology · 2021Review
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Currarino syndrome: a comprehensive genetic review of a rare congenital disorder.Orphanet journal of rare diseases · 2021Review
- MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5.Molecular medicine reports · 2021Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 8 institutions in 4 countries.
Funding
Abstract
We have identified an ethylnitrosourea (ENU)-induced recessive mouse mutation (Vcc) with a pleiotropic phenotype that includes cardiac, tracheoesophageal, anorectal, anteroposterior patterning defects, exomphalos, hindlimb hypoplasia, a presacral mass, renal and palatal agenesis, and pulmonary hypoplasia. It results from a C470R mutation in the proprotein convertase PCSK5 (PC5/6). Compound mutants (Pcsk5(Vcc/null)) completely recapitulate the Pcsk5(Vcc/Vcc) phenotype, as does an epiblast-specific conditional deletion of Pcsk5. The C470R mutation ablates a disulfide bond in the P domain, and blocks export from the endoplasmic reticulum and proprotein convertase activity. We show that GDF11 is cleaved and activated by PCSK5A, but not by PCSK5A-C470R, and that Gdf11-deficient embryos, in addition to having anteroposterior patterning defects and renal and palatal agenesis, also have a presacral mass, anorectal malformation, and exomphalos. Pcsk5 mutation results in abnormal expression of several paralogous Hox genes (Hoxa, Hoxc, and Hoxd), and of Mnx1 (Hlxb9). These include known Gdf11 targets, and are necessary for caudal embryo development. We identified nonsynonymous mutations in PCSK5 in patients with VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb malformation OMIM 192350) and caudal regression syndrome, the phenotypic features of which resemble the mouse mutation. We propose that Pcsk5, at least in part via GDF11, coordinately regulates caudal Hox paralogs, to control anteroposterior patterning, nephrogenesis, skeletal, and anorectal development.
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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.