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Publication : Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo.

First Author  Rongvaux A Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  6 Pages  2378-83
PubMed ID  21262827 Mgi Jnum  J:168301
Mgi Id  MGI:4887927 Doi  10.1073/pnas.1019524108
Citation  Rongvaux A, et al. (2011) Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo. Proc Natl Acad Sci U S A 108(6):2378-83
abstractText  Hematopoietic stem cells (HSCs) both self-renew and give rise to all blood cells for the lifetime of an individual. Xenogeneic mouse models are broadly used to study human hematopoietic stem and progenitor cell biology in vivo. However, maintenance, differentiation, and function of human hematopoietic cells are suboptimal in these hosts. Thrombopoietin (TPO) has been demonstrated as a crucial cytokine supporting maintenance and self-renewal of HSCs. We generated RAG2(-/-)gamma(c)(-/-) mice in which we replaced the gene encoding mouse TPO by its human homolog. Homozygous humanization of TPO led to increased levels of human engraftment in the bone marrow of the hosts, and multilineage differentiation of hematopoietic cells was improved, with an increased ratio of myelomonocytic verus lymphoid lineages. Moreover, maintenance of human stem and progenitor cells was improved, as demonstrated by serial transplantation. Therefore, RAG2(-/-)gamma(c)(-/-) TPO-humanized mice represent a useful model to study human hematopoiesis in vivo.
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