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Fetal liver cells transplanted in utero rescue the osteopetrotic phenotype in the oc/oc mouse.
Fetal liver cells transplanted in utero rescue the osteopetrotic phenotype in the oc/oc mouse.
- Source :
-
The American journal of pathology [Am J Pathol] 2009 Mar; Vol. 174 (3), pp. 727-35. Date of Electronic Publication: 2009 Feb 13. - Publication Year :
- 2009
-
Abstract
- Autosomal recessive osteopetrosis (ARO) is a group of genetic disorders that involve defects that preclude the normal function of osteoclasts, which differentiate from hematopoietic precursors. In half of human cases, ARO is the result of mutations in the TCIRG1 gene, which codes for a subunit of the vacuolar proton pump that plays a fundamental role in the acidification of the cell-bone interface. Functional mutations of this pump severely impair the resorption of bone mineral. Although postnatal hematopoietic stem cell transplantation can partially rescue the hematological phenotype of ARO, other stigmata of the disease, such as secondary neurological and growth defects, are not reversed. For this reason, ARO is a paradigm for genetic diseases that would benefit from effective prenatal treatment. Using the oc/oc mutant mouse, a murine model whose osteopetrotic phenotype closely recapitulates human TCIRG1-dependent ARO, we report that in utero transplantation of adult bone marrow hematopoietic stem cells can correct the ARO phenotype in a limited number of mice. Here we report that in utero injection of allogeneic fetal liver cells, which include hematopoietic stem cells, into oc/oc mouse fetuses at 13.5 days post coitum produces a high level of engraftment, and the oc/oc phenotype is completely rescued in a high percentage of these mice. Therefore, oc/oc pathology appears to be particularly sensitive to this form of early treatment of the ARO genetic disorder.
- Subjects :
- Animals
Crosses, Genetic
DNA Primers
Disease Models, Animal
Female
Fetus
Genotype
Humans
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Osteopetrosis embryology
Osteopetrosis pathology
Phenotype
Polymerase Chain Reaction
Pregnancy
Fetal Tissue Transplantation
Hematopoietic Stem Cell Transplantation
Liver Transplantation
Mutation
Osteopetrosis genetics
Osteopetrosis surgery
Vacuolar Proton-Translocating ATPases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 174
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 19218349
- Full Text :
- https://doi.org/10.2353/ajpath.2009.080688