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.
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.
|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|
|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|
|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|
|Janson, Christopher G; Romanova, Liudmila G; Leone, Paola et al. (2014) Comparison of Endovascular and Intraventricular Gene Therapy With Adeno-Associated Virus-?-L-Iduronidase for Hurler Disease. Neurosurgery 74:99-111|
|Zhao, Gengxiang; Allewell, Norma M; Tuchman, Mendel et al. (2013) Structure of the complex of Neisseria gonorrhoeae N-acetyl-L-glutamate synthase with a bound bisubstrate analog. Biochem Biophys Res Commun 430:1253-8|
|Hackett, Perry B; Largaespada, David A; Switzer, Kirsten C et al. (2013) Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy. Transl Res 161:265-83|
|Wolf, Daniel A; Hanson, Leah R; Aronovich, Elena L et al. (2012) Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration. Mol Genet Metab 106:131-4|
|Wolf, Daniel A; Lenander, Andrew W; Nan, Zhenhong et al. (2011) Direct gene transfer to the CNS prevents emergence of neurologic disease in a murine model of mucopolysaccharidosis type I. Neurobiol Dis 43:123-33|
|Shi, Dashuang; Li, Yongdong; Cabrera-Luque, Juan et al. (2011) A novel N-acetylglutamate synthase architecture revealed by the crystal structure of the bifunctional enzyme from Maricaulis maris. PLoS One 6:e28825|
Showing the most recent 10 out of 72 publications