Homozygotes exhibit peripheral leukocytosis due to an increased number of neutrophils with defective adhesion properties. This mutant mouse strain may be useful in studies of leukocyte adhesion deficiency type I (LADI), and neutrophil adhesion and extravasation.
Christie M. Ballantyne, Baylor College of Medicine
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 (protein) is detected by flow cytometry analysis of isolated neutrophils. Homozygotes exhibit peripheral leukocytosis due to an increased number of neutrophils. Isolated neutrophils do not exhibit increased adhesion to purified ICAM-1 or to endothelial cells. Neutrophil extravasation in response to TNF-alpha is diminished in mutant mice. Isolated neutrophils show decreased attachment strength to endothelial cells as revealed by shear stress detachment tests. This mutant mouse strain may be useful in studies of leukocyte adhesion deficiency type I (LADI), and neutrophil adhesion and extravasation.
A targeting vector containing neomycin resistance gene driven by the mouse RNA polymerase II promoter was used to disrupt a 2.1 kb region containing exons 1 and 2. The construct was electroporated into 129S7/SvEvBrd-Hprtb-m2 derived AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6 blastocysts and chimeric males were mated with C57BL/6 females. The donating investigator stated that the resulting LFA-1 mutant mice (also called Cd11a or Itgal mutant mice) were subsequently backcrossed to C57BL/6 (from Harlan Sprague Dawley) (see SNP note below) for 12 generations prior to arrival at The Jackson Laboratory. Upon arrival, males were bred with C57BL/6J to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Christie M Ballantyne|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Cd11a(-); CD11alpha KO; LFA-1-|
|Gene Symbol and Name||Itgal, integrin alpha L|
|Strain of Origin||129S7/SvEvBrd-Hprtb-m2|
|Molecular Note||Exons 1 and 2 were replaced with a neomycin selection casssette inserted by homologous recombination.|
|Mutations Made By|| |
Huaizhu Wu, Baylor College of Medicine
When maintaining a live colony, these mice are bred as homozygotes.
When using the LFA-1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #005257 in your Materials and Methods section.