Post-natal marrow or peripheral blood stem cell transplantation can effectively treat many genetic disorders which involve blood cells, but is not universally available because of its high cost, moderate risk, and the lack of suitable donors of hematopoietic stem cells. As importantly, in some diseases, such as the lysosomal storage disorders, neurologic toxicity occurs by birth, which is not reversible by transplantation. The investigators plan to study the in utero therapy of alpha-mannosidosis in cats. Besides transplanting hematopoietic stem cells from adult cats to domestic cat fetuses, they propose two novel approaches, the in utero transplantation of macrophage precursor cells and in utero gene transfer (with FeLV-pseudotyped, retroviral vectors containing marker genes and/or MANB cDNA). The investigators will also study the kinetics of tissue macrophage engraftment in a murine ROSA26 transplantation model, to identify the immediate precursor cell of microglia in brain, Kuppffer cells in liver, and alveolar macrophages in lung. The investigators will define the cellular mechanisms which mediate lodgment. The results of experiments in this murine model will be applied in the in utero transplantation studies of alpha-mannosidosis in cats. The investigators are hopeful that these studies will provide alternative approaches for the therapy of lysosomal storage disorders.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZRG3-PBC (01))
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Mckeon, Catherine T
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University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
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