This immunodeficient strain carrying humanized Thpo (thrombopoietin) in addition to Rag2 and Il2rg knock-outs may be useful for transplantation studies, particularly those involving hematopoiesis.
Dr. Richard A. Flavell, Yale University School of Medicine
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Rag2 | recombination activating gene 2 |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Il2rg | interleukin 2 receptor, gamma chain |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Inserted expressed sequence, Humanized sequence) | Thpo | thrombopoietin |
This compound mutant strain carries deletions in the Rag2 and X-linked Il2rg genes in addition to a targeted replacement of mouse Thpo (thrombopoietin) coding sequences with those of the human gene.
Triple homozygotes (hemizygous/homozygous for the Il2rg mutation) lack T, B and NK cells and express human THPO in the same tissues as mouse Thpo, although at a lower concentration. Homozygous humanization of THPO leads to significantly increased levels of human cell engraftment in the bone marrow of hosts, and multilineage differentiation of hematopoietic cells is improved. An increased ratio of myelomonocyte versus lymphoid lineages is also seen. The self-renewal capacity of engrafted human stem and progenitor cells is improved.
The creation of this strain was funded by the Bill and Melinda Gates Foundation.
An embryonic stem (ES) cell line carrying deletions in the Rag2 and Il2rg genes (** below) were re-targeted to place the human thrombopoietin gene (THPO) under the control of the mouse Thpo promoter. A loxP-flanked human ubiquitin promoter (hUBp)-neomycin selection cassette associated with the THPO targeting vector was excised by transient infection with a cre plasmid. This strain was maintained on a mixed BALB/c and 129S4 genetic background by the donating laboratory.
**V17 embryonic stem (ES) cells (derived from BALB/cTac x 129S4/SvJae mice) were used to sequentially delete the coding regions of the Rag2 and X chromosome-linked Il2rg genes. A loxP-flanked PGK-neomycin cassette was targeted to Rag2 and a loxP-flanked human ubiquitin promoter-driven hygromycin cassette was directed to Il2rg. Transient infection with a cre plasmid excised the floxed segments.
Expressed Gene | TPO, thyroid peroxidase, human |
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Site of Expression |
Allele Name | targeted mutation 1.1, Richard A Flavell |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Rag2, recombination activating gene 2 |
Gene Synonym(s) | |
Strain of Origin | BALB/cAnNTac x 129S4/SvJae |
Chromosome | 2 |
General Note | Originally generated in conjunction with Il2rgtm1.1Flv. |
Molecular Note | A floxed PGK-neomycin cassette replaced the coding region. Cre-mediated recombination removed the neo cassette. |
Allele Name | targeted mutation 1.1, Richard A Flavell |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Il2rg, interleukin 2 receptor, gamma chain |
Gene Synonym(s) | |
Strain of Origin | BALB/cAnNTac x 129S4/SvJae |
Chromosome | X |
General Note | Originally generated in conjunction with Rag2tm1.1Flv. |
Molecular Note | A floxed human ubiquitin promoter-driven hygromycin cassette replaced the coding region. Cre-mediated recombination removed the hygro cassette. |
Allele Name | targeted mutation 1.1, Richard A Flavell |
---|---|
Allele Type | Targeted (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | TPOh |
Gene Symbol and Name | Thpo, thrombopoietin |
Gene Synonym(s) | |
Expressed Gene | TPO, thyroid peroxidase, human |
Strain of Origin | BALB/cAnNTac x 129S4/SvJae |
Chromosome | 16 |
General Note | Originally generated in ES cells containing Il2rgtm1.1Flv and Rag2tm1.1Flv. |
Molecular Note | The coding region was replaced with the corresponding human sequence. Cre-mediated recombination removed the neo cassette. |
When maintained as a live colony, animals homozygous for the THPO and Rag2 mutations and also hemizygous/homozygous for X-linked Il2rg mutation may be intercrossed.
When using the Rag2- Il2rg- TPOh mouse strain in a publication, please cite the originating article(s) and include JAX stock #014594 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozyogus for Rag2<tm1.1Flv>, Homozyogus for Thpo<tm1.1(TPO)Flv>, Homozygous and Hemizygous Il2rg<tm1.1Flv> |
Frozen Mouse Embryo | C;129S4-Rag2<tm1.1Flv> Thpo<tm1.1(TPO)Flv> Il2rg<tm1.1Flv>/J | $2595.00 |
Frozen Mouse Embryo | C;129S4-Rag2<tm1.1Flv> Thpo<tm1.1(TPO)Flv> Il2rg<tm1.1Flv>/J | $2595.00 |
Frozen Mouse Embryo | C;129S4-Rag2<tm1.1Flv> Thpo<tm1.1(TPO)Flv> Il2rg<tm1.1Flv>/J | $3373.50 |
Frozen Mouse Embryo | C;129S4-Rag2<tm1.1Flv> Thpo<tm1.1(TPO)Flv> Il2rg<tm1.1Flv>/J | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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