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Transcriptional regulator PRDM12 is essential for human pain perception
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Chen, Ya-Chun
Auer-Grumbach, Michaela
Matsukawa, Shinya
Zitzelsberger, Manuela
Themistocleous, Andreas C
Strom, Tim M
Samara, Chrysanthi
Moore, Adrian W
Cho, Lily Ting-Yin
Young, Gareth T
Fecha
2015
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Nature Publishing Group
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Abstract
Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics. © 2015 Nature America, Inc. All rights reserved.
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Keywords
Isoprotein , human , Unclassified drug , Carrier protein , Nerve protein , Prdm12 protein , Animal cell , Article , Autonomic innervation , Basement membrane , Cell nucleus , Cellular distribution , Chromosome 9 , Chronic pain , Codon , Congenital analgesia , Cornea reflex , Cytoplasm , Differentiation , Embryo , Embryo development , Heterozygote , Histone methylation , Histone modification , Human , In situ hybridization , Missense mutation , Nervous system development , Neural crest cell , Nociception , Nonhuman , Pain receptor , Phenotype , Point mutation , Priority journal , Protein expression , Protein function , Protein interaction , Sensory nerve cell , Sodium current , Sural nerve , Tissue injury , Xenopus , Animal , Chlorocebus aethiops , Consanguinity , Cos 1 cell line , Female , Genetic association , Genetics , Male , Metabolism , Mutation , Neuropathy , Pedigree , Single nucleotide polymorphism , Xenopus laevis , Animals , Carrier proteins , Cercopithecus aethiops , Consanguinity , Cos cells , Female , Genetic association studies , Hereditary sensory and autonomic neuropathies , Humans , Male , Mutation , Nerve tissue proteins , Neurogenesis , Nociceptors , Pain insensitivity , Pain perception , Pedigree , Polymorphism , Xenopus laevis
