article
Transcriptional regulator PRDM12 is essential for human pain perception
Autor
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
Weiss, Caecilia
Schabhüttl, Maria
Stucka, Rolf
Schmid, Annina B
Parman, Yesim
Graul-Neumann, Luitgard
Heinritz, Wolfram
Passarge, Eberhard
Watson, Rosemarie M
Hertz, Jens Michael
Moog, Ute
Baumgartner, Manuela
Valente, Enza Maria
Pereira, Diego
Katona, Istvan
Dusl, Marina
Stendel, Claudia
Wieland, Thomas
Stafford, Fay
Reimann, Frank
von Au, Katja
Finke, Christian
Willems, Patrick J
Nahorski, Michael S
Shaikh, Samiha S
Carvalho, Ofélia P
Nicholas, Adeline K
Karbani, Gulshan
McAleer, Maeve A
Cilio, Maria Roberta
McHugh, John C
Murphy, Sinead M
Irvine, Alan D
Jensen, Uffe Birk
Windhager, Reinhard
Weis, Joachim
Bergmann, Carsten
Rautenstrauss, Bernd
Baets, Jonathan
De Jonghe, Peter
Reilly, Mary M
Kropatsch, Regina
Kurth, Ingo
Chrast, Roman
Michiue, Tatsuo
Bennett, David L H
Woods, C Geoffrey
Senderek, Jan
Restrepo, Carlos M.
Institución
Resumen
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.