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B-NDG hTHPO mice
Strain Name 

NOD.CB17-PrkdcscidIl2rgtm1Thpotm1(THPO)/Bcgen

Common Name 


B-NDG hTHPO mice


Background B-NDG Catalog number  110590
Related Genes 


THPO  (thrombopoietin)


Description


Human HSC (hematopoietic stem cells ) engrafted humanized mice are a powerful model allows researchers to examine the human immune system and related primates' alien virus research and cellular immunotherapy preclinical evaluation. However, maintenance, differentiation, and function of human hematopoietic cells are suboptimal in these hosts. Thrombopoietin (THPO) has been demonstrated as a crucial cytokine supporting maintenance and self-renewal of HSCs.

Biocytogen developed the B-NDG hTHPO mice in which we replaced the gene encoding mouse Thpo by its human CDS region. This mouse combines a B-NDG mouse background and expresses human THPO protein. Homozygous humanization of THPO 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, B-NDG hTHPO mice represent a useful model to study human hematopoiesis in vivo.


General  information

Genomic organization and expression of the Thpo gene


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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


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Strain specific analysis of THPO gene expression in C57BL/6 mice, B-NDG mice and B-NDG hTHPO mice by RT-PCR. Mouse Thpo mRNA was detectable in liver and kidney of C57BL/6 mice (+/+) and B-NDG mice(+/+). Human THPO mRNA was detectable only in homozygous B-NDG hTHPO mice but not in wild-type mice and B-NDG mice.


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

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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.

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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.

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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.

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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.


References
  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