Multicellular living organisms and unmodified parts thereof and – Nonhuman animal
Patent
1995-04-05
1997-12-16
Stanton, Brian R.
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
435 6, 4351723, 43524021, 435 34, 435 70, 800 2, 800DIG2, 800DIG4, 536 235, C07H 2104, C12N 506, C12N 1506, C12Q 168
Patent
active
056987668
ABSTRACT:
A transgenic, non-human animal model is disclosed which lacks receptors which mediate some of the central nervous system (CNS) actions of serotonin. The animal is preferably from a genus selected from the group consisting of Mus (e.g., mice), Rattus (e.g., rats), Oryctologus (e.g., rabbits) and Mesocricetus (e.g., hamsters). More preferably the animal is a mouse which lacks 5HT.sub.2c receptors. Animals lacking such receptors are overweight due to abnormal control of feeding behavior and are prone to spontaneous death from seizures. Thus, such animals provide an animal model for the testing of drugs which are potentially useful in the treatment of eating disorders and diseases such as epilepsy which result in seizures.
REFERENCES:
patent: 4873191 (1989-10-01), Wagner et al.
patent: 4985352 (1991-01-01), Julius et al.
patent: 5387742 (1995-02-01), Cordell
Fields, H. (1984). Advances in Pain Research and Therapy 6, 241-252.
Milatovich et al (1992). Human Mol. Gen. 1, 681-684.
Hartig, P. et al (1990). "The 5-HT.sub.1C Receptor" in Annals of the N.Y. Academy of Sciences, vol. 600, pp. 149-167.
Heath, J. et al (1995). Current Biology 5(9), 997-999.
Curzon, G. (1990). "Serotonin and Appetite" in Annals of the N.Y. Academy of Sciences, vol. 600, 521-531.
Leibowitz, S. (1995). Obesity Research 3, Suppl. 4, 5735-5895. (Abstract only).
Bradley, A. et al (1992). BioTechnology, 10, 534-539.
Lucas, J. et al (1995). Trends in Pharmacological Sciences 16, 246-252.
Kao, H-T et al (1992). FEBS Letters, 307 (3), 324-328.
Sandou, F. et al (1994) Science 265, 1875-1877.
Yu, L et al (1991). Molecular Brain Research 11, 143-9.
Sambrook, J. et al (1989). Molecular Cloning, A Laboratory Manual, 2nd ed. pp. 15.51-15.52.
Orloff et al., "Timed Intravenous Infusion of Metrazol and Strychnine for Testing Anticonvulsant Drugs" Proc. Soc. Exper. Biol. Med. 70:254-257 (Jan.-Apr. 1949).
Jobe et al., "Role of Brain 5-Hydroxytryptamine in Audiogenic Seizure in the Rat" Life Sciences 13:1-13 (1973).
Kilian and Frey, "Central Monoamines and Convulsive Thresholds in Mice and Rats" Neuropharmacology 12:681-692(1973).
Samanin et al., "m-Chlorophenylpiperazine: A Central Serotonin Agonist Causing Powerful Anorexia in Rats," Schm. Arch. Pharmacol. 308:159-163 (1979).
White and Neuman, "Facilitation of Spinal Motoneurone Excitability by 5-HY-Droxytryptamine and Noradrenaline" Brain Research 188:119-127 (1980).
Kravitz et al., "Amines and a Peptide as Neurohormones in Lobsters: Actions on Neuromuscular Preparations and Preliminary Behavioural Studies" J. Exp. Biol. 89:159-175 (1980).
Aghajanian, G. K., "The Modulatory Role of serotonin at Multiple Receptors in Brain" (MIT Press, Cambridge Mass., 1981) pp. 156-185.
Siegelbaum et al., "Serotonin and Cyclic AMP Close Single K.sup.+ Channels in Aplysia Sensory Neurones" Nature 299:413-417 (Sep. 1982).
Gundersen et al., "Serotonin Receptors Induced by Exogenous Messenger RNA in Xenopus Oocytes" Proc. R. Soc. Lond. 219:103-109 (1983).
Jacobs, B.L., "Postsynaptic Serotonergic Action of Hallucinogens," Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives, pp. 183-202 (1984).
de Courcelles et al. "Evidence That Phospholipid Turnover Is the Signal Transducing System Coupled to Serotonin-S.sub.2 Receptor Sites" J. Biol. Chem. 260:7603-7608 (Jun. 1985).
Takaki, J. et al., "Specific Antagonism of Enteric Neural Serotonin Receptors by Dipeptides of 5-Hydroxytryptophan: Evidence that Serotonin Is a Mediator of Slot Synaptic Excitation in the Myenteric Plexus" J. Neuroscience 5:1769-1780 (Jul. 1985).
Sparks and Buckholtz, "Combined Inhibition of Serotonin Uptake and Oxidative Deamination Attenuates Audiogenic Seizures in DBA/2J Mice" Pharmacology Biochem. & Behav. 23:753-757 (Nov. 1985).
Weiss et al., "Serotonin 5-HT, Receptors Mediate Inhibition of Cycle AMP Production in Neurons" European J. of Pharm. 120:227-230 (Jan. 1986).
Conn et al., "A Unique Serotonin Receptor in Choroid Plexus is Linked to Phosphatidylinositol Turnover" Proc. Natl. Acad. Sci. 83:4086-4088 (May 1986).
Andrade et al., "A G Protein Couples Serotonin and GABA.sub.B Receptors to the Same Channels in Hippocampus" Science 234:1161-1300 (Dec. 1986).
De Vivo and Maayani, "Characterization of the 5-Hydroxytryptamine.sub.1A Receptor-Mediated Inhibition of Forskolin-Stimulated Adenylate Cyclase Activity in Guinea Pig and Rat Hippocampal Membranes.sup.1 " J. Pharmacol. and Exper. Ther. 238:248-253 (1986).
Lubbert et al., "Rat Brain 5-HT.sub.1C Receptors Are Encoded by a 5-6 kbase mRNA Size Class and Are Functionally Expressed in Injected Xenopus Oocytes" J. Neuroscience 7(4):1159-1165 (Apr. 1987).
Takahashi et al., "Rat Brain Serotonin Receptors in Xenopus Oocytes are Coupled by Intracellular Calcium to Endogenous Channels" Proc. Natl. Acad. Sci. 84:5063-5067 (Jul. 1987).
Andrade and Nicoll, "Pharmacologically Distinct Actions of Serotonin on Single Pyramidal Neurones of the Rat Hippocampus Recorded In Vitro" J. Physiol. 394:99-124 (1987).
Hoyer and Schoeffter, "5-HT.sub.1D Receptor-mediated Inhibition of Forskolin-stimulated Adenylate Cyclase Activity in Calf Substantia Nigra" European J. of Pharmacol. 147:145-147 (Feb. 1988).
Thomas et al., "The Expression of Transthyretin mRNA in the Developing Rat Brain" Develop. Biol. 128:415-427 (1988).
Peroutka, Stephen J., "5-Hydroxytryptamine Receptor Subtypes" Ann. Rev. Neurosci. 11:45-60 (1988).
Mansour et al., "Disruption of the Proto-oncogene int-2 in Mouse Embryo-derived Stem Cells: A General Strategy for Targeting Mutations to Non-selectable Genes" Nature 336:348-352 (Nov. 1988).
Parkinson and Weingarten "Dissociative Analysis of Ventromedial Hypothalamic Obesity Syndrome" Am. Phys. Soc. 259:R829-R835 (Oct. 1990).
Kennett & Curzon, "Potencies of Antagonists Indicate that 5-HT.sub.1C Receptors Mediate 1-3(chlorophenyl)piperazine-induced Hypophagis" Br. J. Pharmacol. 103:2016-2020 (Aug. 1991).
Sleight et al., "Serotonin Receptor Subtypes: Basic and Clinical Aspects" (eds. Peroutka, S.J.) 211-227 (Wiley-Liss, New York, NY (1991).
Himms-Hagen, "Neural Control of Brown Adipose Tissue Thermogenesis, Hypertrophy, and Atrophy," Frontiers in Neuroendocrinology 12:38-93 (1991).
Blunell, "Serotonin and the biology of feeding," Am. J. Clin. Nutr. 55:155S-159S (1992).
Tecott et al., "Nervous System Distribution of the Serotonin 5-HT.sub.3 Receptor mRNA" Proc. Natl. Acad. Sci. 90:1430-1434 (Feb. 1993).
Kitchener and Dourish, "An Examination of the Behavioural Specificity of Hypophagia Induced by 5-HT.sub.1B, 5-HT.sub.1C and 5-HT.sub.2 Receptor Agonists Using the Post-prandial Satiety Sequence in Rats" Psychopharm. 113:369-377 (Jan. 1994).
Friedman and Leibel, "Tackling a Weighty Problem" Cell 69:217-220 (Apr. 1992).
Tecott and Julius, "A New Wave of Serotonin Receptors" Current Opin. Neurobiol. 3:310-315 (Jun. 1993).
Wurtman et al., "Dexfenfluramine, Fluoxetine, and Weight Loss Among Female Carbohydrate Cravers" Neuropsychopharm. 9:201-210 (1993).
Pompeiano et al., "Distribution of the Serotonin 5-HT.sub.2 Receptor Family mRNAs: Comparison between 5-HT.sub.2A and 5-HT.sub.2C Receptors" Mol. Brain Res. 23:163-178 (1994).
Flier, Jeffrey, "The Adipocyte: Storage Depot or Node on the Energy Information Superhighway" Cell 80:15-18 (Jan. 1995).
Brake et al., "New Structural Motif for Ligand-gated Ion Channels Defined by an Ionotropic ATP Receptor" Nature 371:519-523 (Oct. 1994).
Julius David J.
Sun Linda M.
Tecott Laurence H.
Axelrod Nancy
Bozicevic Karl
Sherwood Pamela J.
Stanton Brian R.
The Regents of the University of California
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