These Zap70 knock-out mice exhibit arrest of Thymic development at the CD4+/CD8+ Double Positive stage.
Dr. Arthur Weiss, University of California, San Francisco
Mice that are homozygous null for the Zap70 gene are viable, fertile, and are immunodeficient. No Zap70 gene product (protein) is immunodetected in the thymocytes of homozygous mice. An intermediate level of expression was immunodetected in the thymocytes of heterozygous mice. Thymic development is arrested at the CD4+/CD8+ Double Positive stage. No peripheral T lymphocytes are detected. Fewer dendritic epidermal T cells were immunodetectable, and those present have an abnormal morphology. This mutant mouse strain represents a model that may be useful in studies related to a rare autosomal recessive form of human SCID as well as thymic development.
A targeting vector containing neomycin resistance and thymidine kinase genes was used to delete approximately 2kb of the Zap70 gene sequence that encodes amino acids 221-520 and includes the C-terminal SH2 domain. The construct was transfected into 129X1/SvJ-derived JM1 embryonic stem cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J.
|Allele Name||targeted mutation 1, Arthur Weiss|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||ZAP-70 -|
|Gene Symbol and Name||Zap70, zeta-chain (TCR) associated protein kinase|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A neomycin resistance cassette replaced a genomic fragment containing sequences corresponding to amino acids 221 to 520, which encode the C-terminal SH2 domain. Western blot analysis on thymocytes derived from homozygous mice confirmed that no detectable protein is expressed from this allele.|
|Mutations Made By|| |
Theresa Kadlecek, University of California, San Francisco
This strain originated and is maintained on a B6;129X background and has been crossed to C57BL/6 at least five times before being made homozygous. Homozygous mice are more susceptible to pathogenic bacteria so conventional specific pathogen-free (SPF) conditions and occasional prophylactic antibiotic treatment are recommended by donating investigator.
When using the ZAP-70 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004225 in your Materials and Methods section.