Abstract

The major objectives of this research proposal are 1) to study mechanisms that control erythropoietin (Ep) production and erythropoiesis in the mammalian fetus, 2) to investigate factors that favor hepatic rather than renal Ep formation, 3) to evaluate the kinetics (delay or acceleration) of the liver-kidney switch of Ep formation, and 4) to assess the in vivo effects of various agents and conditions on the type (fetal or adult) and relative concentration of hemoglobin in different hematopoietic organs during fetal growth and development. These studies will be performed in fetal, newborn and adult sheep before and after treatment with androgens and thyroid hormones; following induction of chronic anemia and polycythemia, chronic partial hepatectomy and/or bilateral nephrectomy, and thyroid gland ablation. In addition, the influence of maternal hypoxia on erythropoiesis in normal and polycythemic fetuses will be investigated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL040722-13
Application #
3358008
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1987-09-05
Project End
1992-09-04
Budget Start
1991-09-05
Budget End
1992-09-04
Support Year
13
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Nevada Reno
Department
Type
Schools of Medicine
DUNS #
146515460
City
Reno
State
NV
Country
United States
Zip Code
89557

  Publications

Tsai, Emily J; Malech, Harry L; Kirby, Martha R et al. (2002) Retroviral transduction of IL2RG into CD34(+) cells from X-linked severe combined immunodeficiency patients permits human T- and B-cell development in sheep chimeras. Blood 100:72-9
Tran, N D; Porada, C D; Almeida-Porada, G et al. (2001) Induction of stable prenatal tolerance to beta-galactosidase by in utero gene transfer into preimmune sheep fetuses. Blood 97:3417-23
Porada, C D; Tran, N D; Zhao, Y et al. (2000) Neonatal gene therapy. transfer and expression of exogenous genes in neonatal sheep following direct injection of retroviral vectors into the bone marrow space. Exp Hematol 28:642-50
Tran, N D; Porada, C D; Zhao, Y et al. (2000) In utero transfer and expression of exogenous genes in sheep. Exp Hematol 28:17-30
Zanjani, E D; Almeida-Porada, G; Livingston, A G et al. (1999) Engraftment and multilineage expression of human bone marrow CD34- cells in vivo. Ann N Y Acad Sci 872:220-31;discussion 231-2
Zanjani, E D; Almeida-Porada, G; Livingston, A G et al. (1998) Human bone marrow CD34- cells engraft in vivo and undergo multilineage expression that includes giving rise to CD34+ cells. Exp Hematol 26:353-60
Zanjani, E D; Almeida-Porada, G; Ascensao, J L et al. (1997) Transplantation of hematopoietic stem cells in utero. Stem Cells 15 Suppl 1:79-92; discussion 93
Zanjani, E D; Almeida-Porada, G; Flake, A W (1996) The human/sheep xenograft model: a large animal model of human hematopoiesis. Int J Hematol 63:179-92
Flake, A W; Hendrick, M H; Rice, H E et al. (1995) Enhancement of human hematopoiesis by mast cell growth factor in human-sheep chimeras created by the in utero transplantation of human fetal hematopoietic cells. Exp Hematol 23:252-7
Zanjani, E D; Srour, E F; Hoffman, R (1995) Retention of long-term repopulating ability of xenogeneic transplanted purified adult human bone marrow hematopoietic stem cells in sheep. J Lab Clin Med 126:24-8

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