@article{60705b78e1ac409ea35a0cc6eec3f04a,
title = "Loss of Prdm12 during development, but not in mature nociceptors, causes defects in pain sensation",
abstract = "Prdm12 is a key transcription factor in nociceptor neurogenesis. Mutations of Prdm12 cause congenital insensitivity to pain (CIP) from failure of nociceptor development. However, precisely how deletion of Prdm12 during development or adulthood affects nociception is unknown. Here, we employ tissue- and temporal-specific knockout mouse models to test the function of Prdm12 during development and in adulthood. We find that constitutive loss of Prdm12 causes deficiencies in proliferation during sensory neurogenesis. We also demonstrate that conditional knockout from dorsal root ganglia (DRGs) during embryogenesis causes defects in nociception. In contrast, we find that, in adult DRGs, Prdm12 is dispensable for most pain-sensation and injury-induced hypersensitivity. Using transcriptomic analysis, we find mostly unique changes in adult Prdm12 knockout DRGs compared with embryonic knockout and that PRDM12 is likely a transcriptional activator in the adult. Overall, we find that the function of PRDM12 changes over developmental time.",
keywords = "DRG, Prdm12, behavior, congenital insensitivity to pain, mouse, nociceptors, pain, painlessness, sensory neurogenesis",
author = "Landy, {Mark A.} and Megan Goyal and Casey, {Katherine M.} and Chen Liu and Lai, {Helen C.}",
note = "Funding Information: This work was supported by F31 NS111796 and the William F. and Grace H. Kirkpatrick award to M.A.L.; NIH R01 DK114036 to C.L.; the Rita Allen Foundation Award in Pain; the Welch Foundation; the President's Research Council Award; the Kent Waldrep Foundation; and NIH R01 NS100741 to H.C.L. We thank Thomas Jessell for the RUNX3 antibody; Tou Yia Vue for help with EdU staining; Fan Wang for the AdvillinCre/+ mice; the UTSW Microarray Core Facility, UTSW Transgenic Core Facility, Neuroscience Microscopy Facility supported by the UTSW Neuroscience Department, and the UTSW Peter O'Donnell, Jr. Brain Institute; Stephanie Shiers, Rahul K. Kollipara, and the Johnson laboratory for technical assistance; Saida Hadjab and Vanja Nagy for helpful discussions; and Ted Price and Jane Johnson for critical reading of the manuscript. H.C.L. designed and supervised the study. M.A.L. designed and performed the experiments; M.G. and K.M.C. assisted with immunostaining experiments and microscopy analysis. C.L. generated and provided the Prdm12F/F mice before publication. M.A.L. and M.G. prepared the figures. M.A.L. and H.C.L. wrote the paper with input from all other authors. The authors declare no competing interests. We worked to ensure sex balance in the selection of non-human subjects. Funding Information: This work was supported by F31 NS111796 and the William F. and Grace H. Kirkpatrick award to M.A.L.; NIH R01 DK114036 to C.L.; the Rita Allen Foundation Award in Pain; the Welch Foundation ; the President{\textquoteright}s Research Council Award; the Kent Waldrep Foundation ; and NIH R01 NS100741 to H.C.L. We thank Thomas Jessell for the RUNX3 antibody; Tou Yia Vue for help with EdU staining; Fan Wang for the Advillin Cre/+ mice; the UTSW Microarray Core Facility, UTSW Transgenic Core Facility, Neuroscience Microscopy Facility supported by the UTSW Neuroscience Department, and the UTSW Peter O{\textquoteright}Donnell, Jr., Brain Institute; Stephanie Shiers, Rahul K. Kollipara, and the Johnson laboratory for technical assistance; Saida Hadjab and Vanja Nagy for helpful discussions; and Ted Price and Jane Johnson for critical reading of the manuscript. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = mar,
day = "30",
doi = "10.1016/j.celrep.2021.108913",
language = "English (US)",
volume = "34",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}