The primary objective of the Animal Hypoxia (Core C) is to provide standardized chronic exposures of sustained and intermittent hypoxia and/or hypercapnia to flies and mice used by all of the Projects, and to characterize the essential respiratory and cardiovascular phenotypes in the different species, genotypes, and exposures studied by the individual Projects. Standardizing exposure is vital for integrating the findings between the different Projects and optimizing data sharing. Centralizing this also insures quality control and dissemination of any results from individual Projects suggesting that the exposure protocols should be adjusted. Importantly, this centralization also conserves animals and resources to maximize the budget and animal sacrifice. Behavioral measurements are not included in this revised proposal but the larger Biospherix chambers, which house multiple animals and cages will be used for all chronic exposures to insure identical social interactions and conditioning. Phenotyping mice in the core also minimizes the cost and maximizes the information individual animal models in terms of the basic metabolic, respiratory and cardiovascular physiology that is necessary for all of the individual Projects. Given the challenges of maintaining disease free-breeding colonies for multiple lines of transgenic mice, it is most efficient and cost effective to make non-invasive and non-terminal descriptive measurements within a physiology core facility before distributing chronically exposed animals to individual laboratories for the actual experiments. Physiological data will be uploaded to a database developed with Systems Biology Core B for all the investigators to use so the projects can focus on the biology. Training in the physiological techniques used to phenotype the animals will also be provided by Core C to predoctoral students and postdoctoral fellows working in the individual Projects.

Public Health Relevance

Chronic hypoxemia is a large health problem with many cardiovascular and lung diseases. For example, sustained (continuous) hypoxemia occurs with emphysema and intermittent hypoxemia occurs with sleepdisordered breathing. The health impact of intermittent hypoxia is especially large considering sleepdisordered breathing occurs in at least 2-4% of adults. Understanding the genetic and physiological basis of tolerance and susceptibility tochronic hypoxia is necessary to improve treatment of these diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL098053-03
Application #
8376862
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$293,112
Indirect Cost
$105,763
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Zanon, Alessandra; Kalvakuri, Sreehari; Rakovic, Aleksandar et al. (2017) SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila. Hum Mol Genet 26:2412-2425
Zarndt, Rachel; Walls, Stanley M; Ocorr, Karen et al. (2017) Reduced Cardiac Calcineurin Expression Mimics Long-Term Hypoxia-Induced Heart Defects in Drosophila. Circ Cardiovasc Genet 10:
Azad, Priti; Zhao, Huiwen W; Cabrales, Pedro J et al. (2016) Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge's disease. J Exp Med 213:2729-2744
Gan, Zhuohui; Fu, Zhenxing; Stowe, Jennifer C et al. (2016) A Protocol to Collect Specific Mouse Skeletal Muscles for Metabolomics Studies. Methods Mol Biol 1375:169-79
Hartley, Paul S; Motamedchaboki, Khatereh; Bodmer, Rolf et al. (2016) SPARC-Dependent Cardiomyopathy in Drosophila. Circ Cardiovasc Genet 9:119-29
Pamenter, Mathhew E; Powell, Frank L (2016) Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis. Compr Physiol 6:1345-85
Dewan, Sukriti; McCabe, Kimberly J; Regnier, Michael et al. (2016) Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study. J Phys Chem B 120:8264-75
Díaz-Trelles, Ramón; Scimia, Maria Cecilia; Bushway, Paul et al. (2016) Notch-independent RBPJ controls angiogenesis in the adult heart. Nat Commun 7:12088
Song, Shanshan; Jacobson, Krista N; McDermott, Kimberly M et al. (2016) ATP promotes cell survival via regulation of cytosolic [Ca2+] and Bcl-2/Bax ratio in lung cancer cells. Am J Physiol Cell Physiol 310:C99-114
Basaran, Kemal Erdem; Villongco, Michael; Ho, Baran et al. (2016) Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans. PLoS One 11:e0146087

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