Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by Northern blot analysis from spleen tissue. Homozygotes exhibit reduced basal IgG1 and IgG2a levels. When challenged with keyhole limpet hemocyanin coupled to DNP, production of IgG2a and IgG3 was 10% and 6% of the wildtype response after primary and secondary challenges, respectively. DNP-Ficoll challenge results in a 90% reduction of IgM and IgA production. Cultured B-cells have diminished proliferation in response to surface IgM stimulation. Keratoconjunctivitis sicca (dry eyes) occurs in 10% of homozygotes aged 6 to 10 months, and in 80% of mice more than 1 year in age. Tear and saliva flow volume is reduced. Histological analysis reveals lymphocyte infiltration and tissue degradation in lachrymal and salivary glands. Mutants older than 1 year in age produce autoantibodies, anti-SSA and anti-SSB. This mutant mouse strain may be useful in studies of primary Sjogren syndrome.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 1 and 2 and part of exon 3. The construct was electroporated into 129S4/SvJaeSor derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for 11 generations.
|Allele Name||targeted mutation 1, Yuan Zhuang|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Id3, inhibitor of DNA binding 3|
|Strain of Origin||129S4/SvJaeSor|
|Molecular Note||The first 2 exons and part of exon 3 were replaced by a PGK neomycin cassette. Gene disruption was confirmed by Northern blot analysis.|
|Mutations Made By|| |
Yuan Zhuang, Duke University Medical Center
When maintaining a live colony, these mice are bred as homozygotes. Homozygous mice begin to exhibit an autoimmune phenotype at 6 months of age.
When using the Id3 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006301 in your Materials and Methods section.