Mice that are homozygous for the Itgamtm1Myd targeted mutation are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. No Itgam protein is detected in homozygous mutant neutrophils. Homozygous null animals have a diminished ability to clear thioglycollate-induced neutrophils, have reduced mast cell numbers in the dorsal skin and peritoneal wall/cavity, and are less susceptible to cerebral ischemia/reperfusion injury. Neutrophils from these animals are deficient at spreading, phagocytosing complement-opsonized particles, and in several Fc-mediated functions. They also exhibit impaired oxidative burst and a diminished responsiveness in LPS- and taxol-mediated gene expression.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a region of the Itgam gene encoding the translational initiation codon and 15 amino acids of the signal peptide. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into 3.5 day C57BL/6 blastocysts and chimeric animals obtained.
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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 43 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice are on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Tanya N Mayadas|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CD11b KO; CD11b/CD18 deficiency; Cd11b-; CR3-; Itgamtm1Tmn; Mac-1-|
|Gene Symbol and Name||Itgam, integrin alpha M|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Replacement of the exon encoding the translational initiation codon and 15 amino acids of the signal peptide with a neomycin cassette.|
|Mutations Made By|| |
Tanya Mayadas, Brigham and Women's Hosp/Harvard Med Sch
This strain originated on a B6;129S4 background and has been backcrossed to C57BL/6 for at least ten generations. When maintaining a homozygous colony, the donating investigator advises replacing breeders every six months with the offspring from heterozygous matings, avoiding sibling matings. Coat color expected from breeding:Black
When using the B6.129S4-Itgamtm1Myd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #003991 in your Materials and Methods section.