D2.129S2(B6)-Cd4^tm1Mak/J

Stock number: 036513
Product name: DBA/2J CD4 KO, Cd4^tm1Mak

Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

DBA/2J CD4 KO mice harbor a Cd4 (CD4 antigen) knock-out allele on a DBA/2J genetic background that is permissive to Kaposi's sarcoma-associated herpesvirus (KSHV). This model has been useful as a syngeneic mouse tumor model for KSHV-induced malignancies involving KSHV-infected DBA/2J cells (unpublished June, 2021).

Detailed description

Kaposi's sarcoma-associated herpesvirus (KSHV)-induced malignancies are common and disproportionately affect HIV-positive individuals.

DBA/2J CD4 KO mice, derived from a backcross of C57BL/6 background Stock No. 002663, harbor a Cd4 (CD4 antigen) knock-out allele on a DBA/2J genetic background that is permissive to KSHV. This model has been useful as a syngeneic mouse tumor model for KSHV-induced malignancies involving KSHV-infected DBA/2J cells (unpublished June, 2021).

No overt baseline phenotypic differences have been observed in these DBA/2J animals, as compared to Cd4 knock-out mice on other genetic backgrounds.

On the original C57BL/6 genetic background, mice homozygous for the Cd4^tm1Mak targeted mutation have a significant block in CD4⁺ T cell development; 90% of their circulating T-cells are CD8⁺. Cell surface expression of CD4 protein is not detected on thymocytes and lymph node cells from homozygous mice. Homozygous mutant mice also show a Class II restricted deficit in helper T-cell activity and other T-cell responses. This mutant mouse strain may be useful in studies of T cell development, susceptibility to viral infection, and inflammation.

Development

This DBA/2J CD4 KO strain was created by backcrossing B6.129S2-Cd4^tm1Mak/J (Stock No. 002663) to DBA/2J (Stock No. 000671) for 8 generations.

To create the original Stock No. 002663, a targeting vector containing a PGK-neo cassette was used to disrupt exon 5. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The mice were crossed to C57BL/6 mice for 8 generations prior to arrival. As of 2018, this colony was backcrossed to C57BL/6 for a total of at least 10 generations.

Allele

Symbol: Cd4^tm1Mak
Name: targeted mutation 1, Tak Mak
MGI accession ID: MGI:1857144
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: CD4-; CD4 KO; CD4⁰
Marker symbol: Cd4
Marker name: CD4 antigen
Marker synonyms: CD4mut; IMD79; L3T4; Leu-3; Ly-4; OKT4D; p55; T4; W3/25
Chromosome: 6
Strain of origin: 129S2/SvPas
Molecular note: A neomycin resistance cassette was inserted into exon 5. Flow cytometry analysis demonstrated that the protein was absent from the cell surface of thymocytes and lymph node cells in homozygous mice.