B6.129S6(Cg)-Id3^tm2.1Zhu/J

Stock number: 024496
Product name: Id3^f
Strain synonyms: Id3^L
Research areas: Cell Biology Research, Research Tools

Description

Id3^f/f floxed mice may be useful for studying the role of T cell development in autoimmune diseases.

Detailed description

These Id3^f/f mutant mice possess loxP sites flanking exons 1-2 of the inhibitor of DNA binding 3 (Id3) gene. ID3 is a dominant negative helix-loop-helix (H-L-H) protein. ID3 forms nonfunctional heterodimers with other HLH proteins, E-proteins in particular, and acts to inhibit the binding of DNA to the other HLH protein. This gene is involved in the regulation of cell cycle progression and B-cell differentiation, and in mediating TCR signals during double positive (DP) to single positive (SP) selection. ID3 deficiencies have been implicated in the development of Sjogren's syndrome, a rheumatic autoimmune disease characterized by persistent dry eyes and mouth, lymphocyte infiltrates in salivary gland, impaired thymocyte selection, and serum positive for multiple autoantibodies. ID3 has also been associated with the onset of Burkitt's lymphoma, a highly aggressive B-cell non-Hodgkin lymphoma. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 1-2 deleted in the cre-expressing tissues or cells.

For example, when bred to mice expressing a T lineage specific Cre recombinase, thymocyte maturation is impaired. These mice develop exocrinopathy starting at two months of age and exhibit high incidence of lymphocyte infiltration to salivary glands between eight and 12 months of age.

Development

A targeting vector was designed to insert a loxP site upstream of exon 1, and a frt-flanked neomycin resistance (neo) cassette followed by a second loxP site downstream of exon 2 of the inhibitor of DNA binding 3 (Id3) gene. The construct was electroporated into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6 mice. Offspring were bred with B6.Cg-Tg(ACTFLPe)9205Dym/J mice (Stock No. 005703) to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. These mice were bred to C57BL/6J mice for at least 10 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Id3^tm2.1Zhu
Name: targeted mutation 2.1, Yuan Zhuang
MGI accession ID: MGI:5009711
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Id3^f; Id3^L
Marker symbol: Id3
Marker name: inhibitor of DNA binding 3
Marker synonyms: bHLHb25; HEIR-1; HLH462; Idb3
Chromosome: 4
Strain of origin: 129S6/SvEvTac
Molecular note: A loxP site was inserted upstream of exon 1. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 2. Flp-mediated recombination removed the neo cassette and left exons 1 and 2 floxed.