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XB-ART-50724
Nat Genet. July 1, 2015; 47 (7): 803-8.

Transcriptional regulator PRDM12 is essential for human pain perception.

Chen YC , Auer-Grumbach M , Matsukawa S , Zitzelsberger M , Themistocleous AC , Strom TM , Samara C , Moore AW , Cho LT , Young GT , Weiss C , Schabhüttl M , Stucka R , Schmid AB , Parman Y , Graul-Neumann L , Heinritz W , Passarge E , Watson RM , Hertz JM , Moog U , Baumgartner M , Valente EM , Pereira D , Restrepo CM , Katona I , Dusl M , Stendel C , Wieland T , Stafford F , Reimann F , von Au K , Finke C , Willems PJ , Nahorski MS , Shaikh SS , Carvalho OP , Nicholas AK , Karbani G , McAleer MA , Cilio MR , McHugh JC , Murphy SM , Irvine AD , Jensen UB , Windhager R , Weis J , Bergmann C , Rautenstrauss B , Baets J , De Jonghe P , Reilly MM , Kropatsch R , Kurth I , Chrast R , Michiue T , Bennett DL , Woods CG , Senderek J .


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.

PubMed ID: 26005867
Article link: Nat Genet.
Grant support: 095698z/11/z Wellcome TrustMedical Research Council , 102645 Wellcome Trust , MR/K000608/1 Medical Research Council , 095698z/11/z Wellcome TrustMedical Research Council , MRC_MR/K000608/1 Medical Research Council , WT102645 Wellcome Trust , 095698z/11/z Wellcome TrustMedical Research Council , 102645 Wellcome Trust , MR/K000608/1 Medical Research Council , 095698z/11/z Wellcome TrustMedical Research Council

Genes referenced: calca ebf3 foxg1 gnl3 isl1 myc neurod4 pax6 pax8 prdm12 six3 vip

Morpholinos referenced: prdm12 MO1

References:
Adzhubei, 2010, Pubmed[+]


Article Images: [+] show captions

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