CD47 deficient mice are useful when studying phagocytosis during inflammation and tumor suppression.
Dr. Frederik Lindberg, Washington University School of Medicine
Mice homozygous for the targeted mutation are viable, fertile, and display no obvious phenotypic abnormalities. Homozygous mutant mice display normal blood counts except for a reduction in the CD3+ fraction of peripheral lymphocytes. Integrin-associated protein (IAP; CD47) expression in heterozygous mice was approximately 40% of wildtype. Intraperitoneal injection of virulent Escherichia coli kills IAP-deficient mice, indicating a defect in the host defense pathway. This response appears to be secondary to both delayed polymorphonuclear leukocyte (PMN) migration to the site of infection and to defective activation at the site. Young CD47-null mice have enhanced physical performance and more efficient metabolism. Skeletal muscle in young (3 month old) CD47-null mice exhibit increased densities of mitochondria (that function normally in terms of ATP production and the activity of the electron transport chain enzymes). CD47-null mice also exhibit increased expression of cytochrome b, cytochrome c, PGC1α and NRF-1.
A targeting vector was designed to replace the IgV domain-encoding exon 2 with a pgk-neomycin resistance cassette. The construct was electroporated into 129S7/SvEvBrd-Hprtb-m2-derived AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6 females to establish the colony.
Mice heterozygous for the mutant allele were crossed to C57BL/6 mice for a total of 15 generations before being sent to The Jackson Laboratory Repository.
|Allele Name||targeted mutation 1, Frederik P Lindberg|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CD47-; IAP-; Itgptm1Fpl|
|Gene Symbol and Name||Cd47, CD47 antigen (Rh-related antigen, integrin-associated signal transducer)|
|Strain of Origin||129S7/SvEvBrd-Hprtb-m2|
|Molecular Note||A neomycin resistance cassette was inserted into exon 2 of the gene, which encodes the signal peptide cleavage site and the IgV domain. Monoclonal antibodies recognizing the Ig domain failed to detect any CD47 antigen on the surface of erythrocytes, bone marrow cells, or other cells including peripheral blood leukocytes, splenocytes, and fibroblasts from homozygous mutant mice. In addition, no antigen was detected in mutant erythrocyte lysates with polyclonal antisera to the NH2 or COOH-termini.|
|Mutations Made By|| |
Dr. Frederik Lindberg, Washington University School of Medicine
When using the IAP- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003173 in your Materials and Methods section.
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