A Phox2b bac transgenic rat line useful for understanding respiratory rhythm generator neural circuitry

Keiko Ikeda, Masanori Takahashi, Shigeru Sato, Hiroyuki Igarashi, Toru Ishizuka, Hiromu Yawo, Satoru Arata, E. Michelle Southard-Smith, Kiyoshi Kawakami, Hiroshi Onimaru

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    The key role of the respiratory neural center is respiratory rhythm generation to maintain homeostasis through the control of arterial blood pCO2/pH and pO2levels. The neuronal network responsible for respiratory rhythm generation in neonatal rat resides in the ventral side of the medulla and is composed of two groups; the parafacial respiratory group (pFRG) and the pre-Bötzinger complex group (preBötC). The pFRG partially overlaps in the retrotra-pezoid nucleus (RTN), which was originally identified in adult cats and rats. Part of the pre-inspiratory (Pre-I) neurons in the RTN/pFRG serves as central chemoreceptor neurons and the CO2sensitive Pre-I neurons express homeobox gene Phox2b. Phox2b encodes a transcription factor and is essential for the development of the sensory-motor visceral circuits. Mutations in human PHOX2B cause congenital hypoventilation syndrome, which is characterized by blunted ventilatory response to hypercapnia. Here we describe the generation of a novel transgenic (Tg) rat harboring fluorescently labeled Pre-I neurons in the RTN/pFRG. In addition, the Tg rat showed fluorescent signals in autonomic enteric neurons and carotid bodies. Because the Tg rat expresses inducible Cre recombinase in PHOX2B-positive cells during development, it is a potentially powerful tool for dissecting the entire picture of the respiratory neural network during development and for identifying the CO2/O2sensor molecules in the adult central and peripheral nervous systems.

    Original languageEnglish
    Article numbere0132475
    JournalPloS one
    Volume10
    Issue number7
    DOIs
    Publication statusPublished - 2015 Jul 6

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General

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  • Cite this

    Ikeda, K., Takahashi, M., Sato, S., Igarashi, H., Ishizuka, T., Yawo, H., Arata, S., Southard-Smith, E. M., Kawakami, K., & Onimaru, H. (2015). A Phox2b bac transgenic rat line useful for understanding respiratory rhythm generator neural circuitry. PloS one, 10(7), [e0132475]. https://doi.org/10.1371/journal.pone.0132475