ArticleThe Journal of clinical investigation2006
Expression of the human PAC1 receptor leads to dose-dependent hydrocephalus-related abnormalities in mice.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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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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
24 citing papers in PubMed, 67 citations in OpenAlex.
- Increased pituitary adenylate cyclase-activating peptide genes expression in the prefrontal cortex in schizophrenia in relation to suicide.Frontiers in molecular neuroscience · 2023Article
- Hydrocephalus in mouse B3glct mutants is likely caused by defects in multiple B3GLCT substrates in ependymal cells and subcommissural organ.Glycobiology · 2021Article
- Multi-omic analysis elucidates the genetic basis of hydrocephalus.Cell reports · 2021Article
- Camel regulates development of the brain ventricular system.Cell and tissue research · 2021Article
- Genes causing congenital hydrocephalus: Their chromosomal characteristics of telomere proximity and DNA compositions.Experimental neurology · 2021Review
- Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss.Frontiers in cellular neuroscience · 2021Article
- Roles for IFT172 and Primary Cilia in Cell Migration, Cell Division, and Neocortex Development.Frontiers in cell and developmental biology · 2019Article
- Primary Cilia-An Underexplored Topic in Major Mental Illness.Frontiers in psychiatry · 2019Review
- Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors.Neurochemical research · 2017Article
- PAC1R agonist maxadilan enhances hADSC viability and neural differentiation potential.Journal of cellular and molecular medicine · 2016Article
- Ins and outs of GPCR signaling in primary cilia.EMBO reports · 2015Review
- In Vivo Expression of the PTB-deleted Odin Mutant Results in Hydrocephalus.Molecules and cells · 2015Article
- Cilia in the choroid plexus: their roles in hydrocephalus and beyond.Frontiers in cellular neuroscience · 2015Article
- Pleiotropic functions of pituitary adenylyl cyclase-activating polypeptide on retinal ontogenesis: involvement of KLF4 in the control of progenitor cell proliferation.Journal of molecular neuroscience : MN · 2014Article
- Article
- Structure and function of the ependymal barrier and diseases associated with ependyma disruption.Tissue barriers · 2014Review
- Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice.PloS one · 2012Article
- Dysregulation of Kruppel-like factor 4 during brain development leads to hydrocephalus in mice.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Behavioral and other phenotypes in a cytoplasmic Dynein light intermediate chain 1 mutant mouse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Role of PACAP in controlling granule cell migration.Cerebellum (London, England) · 2009Review
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8 authors at 1 institution in 1 country.
Funding
Abstract
Hydrocephalus is a common and potentially devastating birth defect affecting the CNS, and its relationship with G protein-coupled receptors (GPCRs) is unknown. We have expressed 2, 4, or 6 copies of a GPCR--the human PAC1 receptor with a 130-kb transgene in the mouse nervous system in a pattern closely resembling that of the endogenous gene. Consistent with PAC1 actions, PKA and PKC activity were elevated in the brains of Tg mice. Remarkably, Tg mice developed dose-dependent hydrocephalus-like characteristics, including enlarged third and lateral ventricles and reduced cerebral cortex, corpus callosum, and subcommissural organ (SCO). Neuronal proliferation and apoptosis were implicated in hydrocephalus, and we observed significantly reduced neuronal proliferation and massively increased neuronal apoptosis in the developing cortex and SCO of Tg embryos, while neurite outgrowth and neuronal migration in vitro remain uncompromised. Ventricular ependymal cilia are crucial for directing cerebrospinal fluid flow, and ependyma of Tg mice exhibited disrupted cilia with increased phospho-CREB immunoreactivity. These data demonstrate that altered neuronal proliferation/apoptosis and disrupted ependymal cilia are the main factors contributing to hydrocephalus in PAC1-overexpressing mice. This is the first report to our knowledge demonstrating that misregulation of GPCRs can be involved in hydrocephalus-related neurodevelopmental 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.