? The purpose of this research resource application (R24) is to provide support for the establishment of a ? canine blood disease models and stem cell (CBDSC) resource. The purpose of the canine blood disease ? models and stem cell resource is to maintain canine models of hemophilia A, hemophilia B, pyruvate kinase ? (PK) deficiency and cyclic hematopoiesis (CH), provide experimental animals for hematology research and ? to provide canine blood, bone marrow, peripheral blood stem cells (PBSCs), hematopoietic progenitor and ? stem cells and technical expertise with the canine model. The objectives of this research resource grant ? are: (1) maintain breeding colonies of hemophilia, PK and CH dogs; (2) provide purpose bred experimental ? animals for collaborative investigation; and (3) provide canine blood and bone marrow stem cells, tissues ? and canine-validated reagents, and assays to qualified investigators. The canine models have been ? maintained in the principal investigator's laboratory for up to 20 years and have been used in collaborative ? studies with NIH funded investigators at multiple institutions but have not been universally available. The ? hemophilia B model is uniquely prone to developing inhibitors making it ideal for gene therapy and ? tolerance studies. The PK deficient dogs are not available elsewhere and the hemophilia A and CH dogs ? are only available in very limited numbers at 1 other institution. Dog leukocyte antigen (DLA), ? histocompatability typing of the breeding colony and experimental animals has been established so that ? DLA identical, haploidentical and mismatched dogs are used in transplantation studies. The dog is a well ? established preclinical model for bone marrow transplantation, cardiac and hemophilia research. Although ? there are numerous NIH supported primate and rodent resources there presently is not a centralized canine ? resource to provide cells, tissues , reagents and specialized support services as a research resource for ? investigators using the canine model. The investigators have more than 30 years combined experience ? with canine blood disease research and are uniquely qualified to establish a canine blood disease and stem ? cell resource. This project will ensure the survival of unique canine blood disease models, provide broader ? access to the models by qualified investigators and establish a centralized resource for canine blood and ? stem cells to address unmet needs in biomedical research community. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Resource-Related Research Projects (R24)
Project #
1R24HL086944-01A1
Application #
7315778
Study Section
Special Emphasis Panel (ZHL1-CSR-A (M2))
Program Officer
Link, Rebecca P
Project Start
2007-07-01
Project End
2012-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
1
Fiscal Year
2007
Total Cost
$335,965
Indirect Cost
Name
University of Alabama Birmingham
Department
Biochemistry
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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Sun, Junjiang; Shao, Wenwei; Chen, Xiaojing et al. (2018) An Observational Study from Long-Term AAV Re-administration in Two Hemophilia Dogs. Mol Ther Methods Clin Dev 10:257-267
Crudele, Julie M; Finn, Jonathan D; Siner, Joshua I et al. (2015) AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice. Blood 125:1553-61
Vallejo, Matthew O; Niemeyer, Glenn P; Vaglenov, Alex et al. (2013) Decreased hematopoietic progenitor cell mobilization in pearl mice. Exp Hematol 41:848-57
Meng, Ronghua; Bridgman, Roger; Toivio-Kinnucan, Maria et al. (2010) Neutrophil elastase-processing defect in cyclic hematopoietic dogs. Exp Hematol 38:104-15
Monahan, Paul E; Lothrop, Clinton D; Sun, Junjiang et al. (2010) Proteasome inhibitors enhance gene delivery by AAV virus vectors expressing large genomes in hemophilia mouse and dog models: a strategy for broad clinical application. Mol Ther 18:1907-16
Niemeyer, Glenn P; Herzog, Roland W; Mount, Jane et al. (2009) Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood 113:797-806