B6.129X1-Zap70^tm1Weis/J

Stock number: 004225
Product name: ZAP-70 KO
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These Zap70 knock-out mice exhibit arrest of Thymic development at the CD4+/CD8+ Double Positive stage.

Detailed description

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.

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

Symbol: Zap70^tm1Weis
Name: targeted mutation 1, Arthur Weiss
MGI accession ID: MGI:2176252
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Zap70
Marker name: zeta-chain (TCR) associated protein kinase
Chromosome: 1
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.