title: A Phox2b BAC Transgenic Rat Line Useful for Understanding Respiratory Rhythm Generator Neural Circuitry.
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 pO2 levels. 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 retrotrapezoid 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 CO2 sensitive 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/O2 sensor molecules in the adult central and peripheral nervous systems.
authors.affiliation: Division of Biology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Physiology, and Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Igarashi
authors.affiliation: Department of Developmental Biology and Neuroscience, Tohoku University Graduate School of Life Sciences and JST/CREST, Sendai, Miyagi, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ishizuka
authors.affiliation: Department of Physiology, and Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; Department of Developmental Biology and Neuroscience, Tohoku University Graduate School of Life Sciences and JST/CREST, Sendai, Miyagi, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Yawo
authors.affiliation: Center for Biotechnology, Showa University, Shinagawa, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Arata
authors.affiliation: Division of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: E Michelle
authors.initials: EM
authors.lastname: Southard-Smith
authors.affiliation: Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Physiology, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onimaru
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000166:cytology / Q000502:physiology; D022202:Chromosomes, Artificial, Bacterial; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D010100:Oxygen / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D051381:Rats; D055647:Rats, Transgenic; D056152:Respiratory Rate / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D065833:Trapezoid Body / Q000166:cytology / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors; D002245:Carbon Dioxide; D010100:Oxygen