Animal Models Core

The overall objective of the Models of Gastrointestinal Function and Disease (MGFD) Core is to provide expertise on in vivo characterization of normal and pathophysiological mechanisms of hormonal and neural regulation of gastrointestinal (GI) function and brain-gut interactions in rodents to members and associate members of the CURE: DDRC. *

*All  Gastrointestinal Function Testing and Disease Models Core services follow federal and local rules and regulations to protect experimental subjects from undue discomfort. Investigators who wish to use the Core must have an approved protocol with the Institutional Animal Care and Use Committee (IACUC) and the Research & Development Office of the VA Greater Los Angeles Healthcare System (VAGLAHS) before experiments can begin.  The protocol must list all personnel who will come into contact with the experimental subjects and/or conduct the experiments.  All personnel listed must be certified by the committee and office above.  Users should contact us before submitting their protocols to determine if the procedures should differ from those already approved for the Core.

 Core Services:

  • Measurement of GI Secretory, Motor, Neural Functions; Food Intake and Body Fat distribution in Conscious Rats and Mice:

    Determination of Gastric Emptying (1; 2)
    Determination of Colonic Motor Function (3)
    Measurement of Visceral Pain (4)
    Functional Mapping of Neuronal Activation at   Cellular Levels (5)
    Monitoring Brain-Gut Interactions through Pharmacological,  
    Immunohistochemical and Genetic Approaches(7; 8)
    Monitoring Microstructure of Food Intake (6)
    Monitoring of body fat ratio using EchofMRI

  • GI Functional and Electrophysiological Measurements in Anesthetized Rodents:

    Gastric and colonic Motility Measurements using Intraluminal Pressure (9) or        Ultrasonomicrometry (10).
    In Vivo Microscopic Preparation and Measurement of Gut Epithelial pH in Mice (11)
    Recording of Gastric and Splanchnic Nerve Activity in Rats (12; 13)

  • Ex-vivo gastrointestinal Function Assay

    Electrophysiology of Esophageal and Intestinal Mucosal Barrier Functions (14)
    Monitoring Enteric Neuron Activity in Whole Mount and Primary Culture (15; 16)

  • Experimental Gl Diseases Models (rats or mice)

    Models of Gastroduodenal Mucosal Defense (17)
    Genetic and Chemical Models of Colitis (18)
    Models of Post-operative Ileus (19; 20)
    Models of Acute and Chronic Stress (4; 21; 22)
    Models of Cephalic, Gastric, and Intestinal Phases of Gastric Secretion in Rats (23 ) 
    Access to Other Genetically Modified Mice via Institutional Shared Resources
    Genetic Model for Chronic Stress with Related Alterations of Gut Motor Function(24)
    Model for Neurodegenerative Diseases with Related Alterations of Gut Motor Function (25)
    Models of Visceral Pain Studies in Rodents (26)
    Non Transgenic Model of Metabolic Diseases in Rats (27)

  • Teaching or Performing Specialized Assay Methods or Use of Specialized Equipments

    Drug Delivery into Specific Brain Regions and through Different Routes
    Use of equipments:  barostat; Ussing’s; Biodaq, electrophysiological recordings; EchofMRI.
    Collection of Body Fluid/Tissues
    Procedures
    Expertise in Experimental Animal Models For Gut Function Studies, Study Design, Data Analysis and Interpretation
    Expertise/Services for Experimental Animal Handling, Procedures And Enteric Immunohistochemistry:

References

   1.   Martinez V, Wang L, Rivier JE, Vale W, Taché Y. Differential actions of peripheral corticotropin-releasing factor (CRF), urocortin II, and urocortin III on gastric emptying and colonic transit in mice:  role of CRF receptor subtypes 1 and 2. J Pharmacol Exp Ther 2002;301:611-617.

   2.   Million M, Maillot C, Saunders PR, Rivier J, Vale W, Taché Y. Human urocortin II, a new CRF-related peptide, displays selective CRF2-mediated action on gastric transit in rats. Am J Physiol Gastrointest Liver Physiol 2002;282:G34-G40.

   3.   Gourcerol G, Wang L, Adelson DW, Larauche M, Taché Y, Million M. Cholinergic giant migrating contractions in conscious mouse colon assessed by using a novel noninvasive solid-state manometry method: modulation by stressors. Am J Physiol Gastrointest Liver Physiol 2009;296:G992-G1002.

   4.   Larauche M, Gourcerol G, Million M, Adelson DW, Taché Y. Repeated psychological stress-induced alterations of visceral sensitivity and colonic motor functions in mice: influence of surgery and postoperative single housing on visceromotor responses. Stress 2010;13:343-354.

   5.   Million M, Wang L, Martinez V, Taché Y. Differential Fos expression in the paraventricular nucleus of the hypothalamus, sacral parasympathetic nucleus and colonic motor response to water avoidance stress in Fischer and Lewis rats. Brain Res 2000;877:345-353.

   6.   Stengel A, Goebel M, Wang L, Rivier J, Kobelt P, Monnikes H, Taché Y. Activation of brain somatostatin 2 receptors stimulates feeding in mice: analysis of food intake microstructure. Physiol Behav 2010;101:614-622.

   7.   Wang L, Martinez V, Vale W, Taché Y. Fos induction in selective hypothalamic neuroendocrine and medullary nuclei by intravenous injection of urocortin and corticotropin-releasing factor in rats. Brain Res 2000;855:47-57.

   8.   Wang L, Cardin S, Martinez V, Taché Y, Lloyd KC. Duodenal loading with glucose induces fos expression in rat brain: selective blockade by devazepide. Am J Physiol 1999;277:R667-R674.

   9.   Gourcerol G, Adelson DW, Million M, Wang L, Taché Y. Modulation of gastric motility by brain-gut peptides using a novel non-invasive miniaturized pressure transducer method in anesthetized rodents. Peptides 2011;32:737-746.

10.   Adelson DW, Million M, Kanamoto K, Palanca T, Taché Y. Coordintated gastric and sphincter motility evoked by intravenous CCK-8 as monitored by ultrasononomicrometry in rats. Am J Physiol Gastrointest Liver Physiol 2004;283:G321-G332.

11.   Kaunitz JD, Akiba Y. Purinergic regulation of duodenal surface pH and ATP concentration: implications for mucosal defence, lipid uptake and cystic fibrosis. Acta Physiol (Oxf) 2011;201:109-116.

12.   Adelson DW, Wei JY, Yashar M, Lee TJ, Taché Y. Central autonomic activation by intracisternal TRH analogue excites gastric splanchnic afferent neurons. J Neurophysiol 1999;81:682-691.

13.   Adelson DW, Kosoyan HP, Wang Y, Steinberg JZ, Taché Y. Gastric vagal efferent inhibition evoked by intravenous CRF is unrelated to simultaneously recorded vagal afferent activity in urethane-anesthetized rats. J Neurophysiol 2007;97:3004-3014.

14.   Hershcovici T, Poh CH, Fass OZ, Ashpole N, Akiba Y, Guillen-Rodriguez JM, Kaunitz JD, Fass R. Oesophageal sensation in response to high PCO(2) and acidic solutions in nonerosive reflux disease. Eur J Clin Invest 2012;42:195-202.

15.   Gourcerol G, Wu SV, Yuan PQ, Pham H, Miampamba M, Larauche M, Sanders P, Amano T, Mulak A, Im E, Pothoulakis C, Rivier J, Taché Y, Million M. Activation of corticotropin-releasing factor receptor 2 mediates the colonic motor coping response to acute stress in rodents. Gastroenterology 2011;140:1586-1596.

16.   Wang L, Martinez V, Kimura H, Taché Y. 5-Hydroxytryptophan activates colonic myenteric neurons and propulsive motor function through 5-HT4 receptors in conscious mice. Am J Physiol Gastrointest Liver Physiol 2007;292:G419-G428.

17.   Kaunitz JD, Akiba Y. Duodenal carbonic anhydrase: mucosal protection, luminal chemosensing, and gastric acid disposal. Keio J Med 2006;55:96-106.

18.   Million M, Taché Y, Anton P. Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis: protective role of brain CRF. Am J Physiol 1999;276:G1027-G1036.

19.   Stengel A, Goebel-Stengel M, Wang L, Shaikh A, Lambrecht NW, Rivier J, Taché Y. Abdominal surgery inhibits circulating acyl ghrelin and ghrelin-O-acyltransferase levels in rats: role of the somatostatin receptor subtype 2. Am J Physiol Gastrointest Liver Physiol 2011;301:G239-G248.

20.   Luckey A, Wang L, Jamieson PM, Basa NR, Million M, Czimmer J, Vale W, Taché Y. Corticotropin-releasing factor receptor 1-deficient mice do not develop postoperative gastric ileus. Gastroenterology 2003;125:654-659.

21.   Bonaz B, Taché Y. Water-avoidance stress-induced c-fos expression in the rat brain and stimulation of fecal output: role of corticotropin-releasing factor. Brain Res 1994;641:21-28.

22.   Larauche M, Bradesi S, Million M, McLean P, Taché Y, Mayer EA, McRoberts JA. Corticotropin-releasing factor type 1 receptors mediate the visceral hyperalgesia induced by repeated psychological stress in rats. Am J Physiol Gastrointest Liver Physiol 2008;294:G1033-G1040.

23.   Martinez V, Barrachina MD, Ohning G, Taché Y. Cephalic phase of acid secretion involves activation of medullary TRH receptor subtype 1 in rats. Am J Physiol Gastrointest Liver Physiol 2002;283:G1310-G1319.

24.   Million M, Wang L, Stenzel-Poore MP, Coste SC, Yuan PQ, Lamy C, Rivier J, Buffington T, Taché Y. Enhanced pelvic responses to stressors in female CRF-overexpressing mice. Am J Physiol Regul Integr Comp Physiol 2006;.292:R1429-R1438.

25.   Wang L, Fleming SM, Chesselet MF, Taché Y. Abnormal colonic motility in mice overexpressing human wild-type alpha-synuclein. NeuroRep 2008;19:873-876.

26.   Larauche M, Gourcerol G, Wang L, Pambukchian K, Brunnhuber S, Adelson DW, Rivier J, Million M, Taché Y. Cortagine, a CRF1 agonist, induces stresslike alterations of colonic function and visceral hypersensitivity in rodents primarily through peripheral pathways. Am J Physiol Gastrointest Liver Physiol 2009;297:G215-G227.

27.   Yang H, Nyby MD, Ao Y, Chen A, Adelson DW, Smutko V, Wijesuriya J, Go VL, Tuck ML. Role of brainstem thyrotropin-releasing hormone-triggered sympathetic overactivation in cardiovascular mortality in type 2 diabetic Goto-Kakizaki rats. Hypertens Res 2012;35:157-165.

Contact Information:

Yvette Tache, PhD,Core Director
Ytache@mednet.ucla.edu
(310) 312-9275

Charalabos Pothoulakis, MD, Core Co-Director
CPothoulakis@mednet.ucla.edu 

Million Mulugeta, DVM, PhD
Core Associate Director
MillionMulugeta@mednet.ucla.edu
(310) 268-3863