NOD.129S4(Cg)-Itga4^tm1Tpa/HbbMmjax

Stock number: 036218
Product name: α4^flox
Research areas: Diabetes and Obesity Research, Research Tools

Description

α4^flox mutant mice possess loxP sites flanking the promoter and first two exons of the Itga4 (integrin alpha 4) gene. The α4^flox allele has been introgressed on to the NOD/ShiLtJ (non-obese diabetic) background and may be useful in generating conditional mutations to study type 1 diabetes.

Detailed description

Itga4 (integrin alpha 4, also known as CD49d) encodes the alpha 4 subunit of integrin, a heterodimeric integral membrane protein involved in cell surface adhesion and signaling and widely expressed in the hematopoietic system. Adhesion molecules that include α4 (and β7) have been identified as immune modulators in several autoimmune diseases. These conditional α4^flox NOD mice possess loxP sites flanking the promoter and first two exons of the Itga4 (integrin alpha 4) gene. Mice homozygous for the mutation are viable and fertile. Diabetes incidence in females is similar to NOD/ShiLtJ females (Stock No. 001976) - 90% by 30 weeks, median incidence in females is 18 weeks. Male diabetes incidence has not been tested. Global germline knock-out of Itga4 results in embryonic lethality. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have Itga4 deleted in cre-expressing tissues.

For example, when bred to mice with Cre recombinase expression in endothelial cells and hematopoietic cells (Tg(Tek-cre)12Flv), resulting offspring are protected from diabetes and insulitis.

Development

The targeting construct was designed to insert a loxP-flanked neomycin cassette into the promoter and a second loxP site downstream of exon 2 of the Itga4 gene. The construct was electroporated into 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Chimeric males were crossed to C57BL/6 females and the strain was maintained on a mixed C57BL/6 and 129 background. Dr. Halvard Bonig (Goethe Institute) obtained the α4^flox mice from Dr. Payayanopoulou (University of Washington) and introgressed the allele into NOD/ShiLtJ for 10 generations. α4^flox mice mice were combined with mice carrying Tg(Tek-cre)12Flv on a congenic NOD background. The transgene was later bred out of the strain. Upon arrival, mice were bred to NOD/ShiLtJ (Stock No. 001976) for at least one generation to establish the colony.

Allele

Symbol: Itga4^tm1Tpa
Name: targeted mutation 1, Thalia Papayannopoulou
MGI accession ID: MGI:2684111
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: alpha4^f; alpha4^flox
Marker symbol: Itga4
Marker name: integrin alpha 4
Marker synonyms: CD49D; IA4; VLA-4 receptor, alpha 4 subunit
Chromosome: 2
Strain of origin: 129S4/SvJaeSor
Molecular note: A floxed PGK-neomycin cassette was inserted in the promoter and an additional loxP site was placed distal to the second exon. Protein product was expressed at the same levels seen in wild-type mice.