NDLI: Prevention of genetic anemias in mice by microinjection of normal hematopoietic stem cells into the fetal placenta.

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Prevention of genetic anemias in mice by microinjection of normal hematopoietic stem cells into the fetal placenta.

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Prevention of genetic anemias in mice by microinjection of normal hematopoietic stem cells into the fetal placenta.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mintz, B. Fleischman, R. A.
Abstract	Mice homozygous for mutant genes at the W locus have a marked macrocytic anemia that is fatal in some genotypes. The defect is believed to originate in the developmentally pluripotent hematopoietic stem cell population. Anemia is first grossly manifest on day 13 of gestation, when the liver is the chief hematopoietic organ. The known paucity of blood-forming foci in livers of homozygotes and the limited formation of their erythrocytes suggested that such fetuses-unlike normal ones-might have conditions favorable for in utero seeding of genetically normal hematopoietic tissue. If this were accomplished before day 13, the anemia might essentially be prevented, or at least substantially mitigated, and normalcy soon achieved by cell selection. This proved to be the case. Allogeneic normal fetal liver cells were microinjected into the blood vessels of the fetal placenta on day 11 of gestation. Of eight mutant homozygotes born from segregating matings, six (four W/W, two W(v)/W(v)) were successfully populated with donor cells. Strain-specific hemoglobin markers demonstrated replacement of the erythroid lineage with the normal type, the rate of substitution being more rapid in the W/W (ordinarily more anemic) recipients. Strain-specific isozyme differences revealed that white blood cells were also replaced. Thus, the initial selective pressure, hence the W-mutant phenotypic lesion, must have occurred at the pluripotent stem cell stage. The animals remained immunologically tolerant of the donor cells and no graft-versus-host reaction occurred. The early introduction of hematopoietic cells differing genetically from all the other tissues of the animal provides possibilities for tracing normal hematopoietic lineages in vivo, for analyzing cell and tissue interactions, such as those between lymphocytes and thymus, and for clarifying the etiology of other blood or immune insufficiencies or malignancies.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	76
Language	English
Publisher	National Academy of Sciences
Publisher Date	1979-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Anemia, Macrocytic Genetics Hematopoietic Stem Cell Transplantation Blood Prevention & Control Animals Hemoglobins, Abnormal Immune Tolerance Mice Microinjections Mosaicism Placenta Cytology Transplantation, Homologous Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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