The objective of the Research Animal Care and Medicine Core is to provide the appropriate animal models and technical and pathology support to the research projects of this grant in a timely and cost-effective manner. The multiple specialized animal models of genetic dysfunction used for each of these projects require expert colony management including animal and veterinary care, breeding management, housing, veterinary preventive medicine and diagnostic support, as well as technical expertise in experimental manipulation of all ages of mice and dogs. Analysis of housing needs, procurement and breeding options, and intensive management and monitoring of in-house mouse production colonies are necessary forthe smooth functioning ofthe specific aims ofthe research projects. The Research Animal Care and Medicine Core will provide veterinary oversight and individualized care and programming for the animal models integral to each project. This Core will interact closely with the other Cores to provide the most appropriate samples for prompt genotyping and individual animal identification. Animal Core staff will also provide technical support (e.g. intravascular administration of rDNA to newborn mice, post-procedural care for mice and dogs, clinical, hematologic and clinical pathologic evaluation of animals on project experiments, therapeutic intervention if necessary, harvesting of brain tissues for evaluation by Core B) and routine research pathology support. Quality control is focused on ensuring the genetic integrity of mice by genotyping and record-keeping and on preventing confounding effects from intercurrent infectious and noninfectious disease. The latter is accomplished by specific pathogen-free housing, by an intensive serology surveillance program to detect the presence of potential pathogens, close monitoring ofthe animals' health, and diagnostic pathology as needed. Prevention of confounding effects of infectious and non- infectious conditions in dogs will be ensured by proper choice of sources of dogs and intensive health monitoring and treatment when appropriate.

Public Health Relevance

Provision of genotypically and phenotypically appropriate animal models and prevention of confounding effects of intercurrent health problems in animal models is crucial to the success ofthe projects in advancing the understanding and treatment of MPS diseases in people.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD032652-16
Application #
8475631
Study Section
Special Emphasis Panel (ZHD1-DSR-Z)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
16
Fiscal Year
2013
Total Cost
$197,544
Indirect Cost
$66,777
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Ou, Li; Przybilla, Michael J; Whitley, Chester B (2016) Proteomic analysis of mucopolysaccharidosis I mouse brain with two-dimensional polyacrylamide gel electrophoresis. Mol Genet Metab :
Ou, Li; Przybilla, Michael J; Koniar, Brenda L et al. (2016) Elements of lentiviral vector design toward gene therapy for treating mucopolysaccharidosis I. Mol Genet Metab Rep 8:87-93
Aronovich, Elena L; Hackett, Perry B (2015) Lysosomal storage disease: gene therapy on both sides of the blood-brain barrier. Mol Genet Metab 114:83-93
Wolf, Daniel A; Banerjee, Sharbani; Hackett, Perry B et al. (2015) Gene therapy for neurologic manifestations of mucopolysaccharidoses. Expert Opin Drug Deliv 12:283-96
Satzer, David; DiBartolomeo, Christina; Ritchie, Michael M et al. (2015) Assessment of dysmyelination with RAFFn MRI: application to murine MPS I. PLoS One 10:e0116788
Ou, Li; Herzog, Tyler; Koniar, Brenda L et al. (2014) High-dose enzyme replacement therapy in murine Hurler syndrome. Mol Genet Metab 111:116-22
Hackett, Perry B; Aronovich, Elena L (2014) Rational design for enhanced gene therapy with DNA transposons. Mol Ther 22:1575-7
Janson, Christopher G; Romanova, Liudmila G; Leone, Paola et al. (2014) Comparison of Endovascular and Intraventricular Gene Therapy With Adeno-Associated Virus-α-L-Iduronidase for Hurler Disease. Neurosurgery 74:99-111
Ou, Li; Herzog, Tyler L; Wilmot, Carrie M et al. (2014) Standardization of *-L-iduronidase enzyme assay with Michaelis-Menten kinetics. Mol Genet Metab 111:113-5
Carpentier, Claire E; Schreifels, Jeffrey M; Aronovich, Elena L et al. (2014) NMR structural analysis of Sleeping Beauty transposase binding to DNA. Protein Sci 23:23-33

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