Image_2_PRDM12 Is Transcriptionally Active and Required for Nociceptor Function Throughout Life.JPEG (817.68 kB)
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Image_2_PRDM12 Is Transcriptionally Active and Required for Nociceptor Function Throughout Life.JPEG

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posted on 27.09.2021, 04:31 by Tomislav Kokotović, Michiel Langeslag, Ewelina M. Lenartowicz, John Manion, Christopher W. Fell, Elham Alehabib, Abbas Tafakhori, Hossein Darvish, Eric J. Bellefroid, G. Gregory Neely, Michaela Kress, Josef M. Penninger, Vanja Nagy

PR domain-containing member 12 (PRDM12) is a key developmental transcription factor in sensory neuronal specification and survival. Patients with rare deleterious variants in PRDM12 are born with congenital insensitivity to pain (CIP) due to the complete absence of a subtype of peripheral neurons that detect pain. In this paper, we report two additional CIP cases with a novel homozygous PRDM12 variant. To elucidate the function of PRDM12 during mammalian development and adulthood, we generated temporal and spatial conditional mouse models. We find that PRDM12 is expressed throughout the adult nervous system. We observed that loss of PRDM12 during mid-sensory neurogenesis but not in the adult leads to reduced survival. Comparing cellular biophysical nociceptive properties in developmental and adult-onset PRDM12 deletion mouse models, we find that PRDM12 is necessary for proper nociceptive responses throughout life. However, we find that PRDM12 regulates distinct age-dependent transcriptional programs. Together, our results implicate PRDM12 as a viable therapeutic target for specific pain therapies even in adults.

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