General  information

Genomic organization and expression of the Thpo gene

Fig. 2 Activation of the TPO receptor by TPO or TPO receptor agonists. TPO and romiplostim bind to the distal cytokine receptor homology domain (CRH-2) of the preformed, inactive TPO receptor dimer. Eltrombopag binds to the transmembrane region of the TPO receptor. Multiple signal transduction pathways are thereby activated.

mRNA expression analysis

B-NDG hTHPO mice are well suited for human immune system engraftment

Human CD34+ cells(5E5) were intravenous implanted into homozygote B-NDG hTHPO and B-NDG mice (female, 6 week-old, n=20). B-NDG mice were treated with 2Gy-irradiation, B-NDG hTHPO mice were not irradiated. Representative flow cytometric analysis of peripheral blood lymphocyte from mice after engraftment with human CD34+ cells. B-NDG hTHPO mice show a higher percentage of survival rate compared with B-NDG.Non-irradiated B-NDG hTHPO mice showed no difference in the percentage of human CD45+ cells compared to B-NDG mice. The results showed that the human HSC (hematopoietic stem cells) engrafted humanized mice model was successfully constructed.

Human CD34+ cells(5E5) were intravenous implanted into homozygote B-NDG hTHPO and B-NDG mice (female, 6 week-old, n=20). B-NDG mice were treated with 2Gy-irradiation, B-NDG hTHPO mice were not irradiated. Representative flow cytometric analysis of peripheral blood lymphocyte from mice after engraftment with human CD34+ cells. Non-irradiated B-NDG hTHPO mice showed no difference in the percentage of human multi-lineage cells compared to B-NDG mice, including T ,B, NK, myeloid cells，monocyte and neutrophils. The results showed that the human HSC (hematopoietic stem cells) engrafted humanized mice model was successfully constructed.

Human CD34+ cells(5E5) were intravenous implanted into homozygote B-NDG hTHPO (female, 6 week-old, n=20). and B-NDG mice (female, 6 week-old, n=17). B-NDG mice were treated with 1.6Gy-irradiation, B-NDG hTHPO mice were not irradiated. Representative flow cytometric analysis of peripheral blood lymphocyte from mice after engraftment with human CD34+ cells. B-NDG hTHPO mice show a higher percentage of survival rate compared with B-NDG. Non-irradiated B-NDG hTHPO mice showed no difference in the percentage of human CD45+ cells compared to B-NDG mice. The results showed that the human HSC (hematopoietic stem cells) engrafted humanized mice model was successfully constructed.

Human CD34+ cells(5E5) were intravenous implanted into homozygote B-NDG hTHPO (female, 6 week-old, n=20). and B-NDG mice (female, 6 week-old, n=17). B-NDG mice were treated with 1.6Gy-irradiation, B-NDG hTHPO mice were not irradiated. Representative flow cytometric analysis of peripheral blood lymphocyte from mice after engraftment with human CD34+ cells. Non-irradiated B-NDG hTHPO mice showed no difference in the percentage of human multi-lineage cells compared to B-NDG mice, including T ,B, NK, myeloid cells，monocyte and neutrophils. The results showed that the human HSC (hematopoietic stem cells) engrafted humanized mice model was successfully constructed.

1. Kuter, D. J. The biology of thrombopoietin and thrombopoietin receptor agonists. International journal of hematology 98, 10-23, doi:10.1007/s12185-013-1382-0 (2013).
2. Rongvaux A, et al., Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo. Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2378-83