Abstract
In utero exposure of the embryo and fetus to radiation has been implicated in malformations or fetal death, and often produces lifelong health consequences such as cancers and mental retardation. Here we demonstrate that deletion of a G-protein-coupled purinergic receptor, P2Y14, confers potent resistance to in utero radiation. Intriguingly, a putative P2Y14 receptor ligand, UDP-glucose, phenocopies the effect of P2Y14 deficiency. These data indicate that P2Y14 is a receptor governing in utero tolerance to genotoxic stress that may be pharmacologically targeted to mitigate radiation toxicity in pregnancy.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Atrophy / prevention & control
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Body Weight / drug effects
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DNA Damage
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Female
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Hydrocephalus / metabolism
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Hydrocephalus / prevention & control*
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Male
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Maternal Exposure
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Mice
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Mice, Knockout
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Pregnancy
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Prenatal Exposure Delayed Effects / metabolism
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Prenatal Exposure Delayed Effects / prevention & control*
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Radiation Injuries, Experimental / metabolism
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Radiation Injuries, Experimental / prevention & control*
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Radiation Tolerance
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Receptors, Purinergic P2 / deficiency
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Receptors, Purinergic P2 / genetics*
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Receptors, Purinergic P2Y
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Spleen / drug effects
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Spleen / pathology
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Uridine Diphosphate Glucose / pharmacology*
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Uridine Diphosphate Glucose / therapeutic use
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Whole-Body Irradiation
Substances
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P2ry14 protein, mouse
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Receptors, Purinergic P2
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Receptors, Purinergic P2Y
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Uridine Diphosphate Glucose