These integrin beta 3 targeted mutant mice exhibit significant embryonic lethality attributed to fetal hemorrhaging and placental defects. This mutant mouse strain represents a model that may be useful in studies related to Glanzmann thrombasthenia.
Dr. Richard Hynes, Massachusetts Institute of Technology
Mice that are homozygous for this targeted allele are viable and fertile. No gene product (protein) is detected on the surface of platelets. Significant (50%) embryonic lethality attributed to fetal hemorrhaging and placental defects is observed. Until three weeks of age, additional pup loss may occur due to hemorrhaging in the skin and gastrointestinal tract. Gastrointestinal tract bleeding is commonly observed in adults and is frequently associated with an enlarged spleen. Erythrocyte number, hemoglobin, hematocrits and thrombus formation are all reduced while bleeding time is prolonged. Varying degrees of liver and kidney necrosis are also observed. Although increased numbers of osteoclasts are observed (3.5 fold over that seen in heterozygotes) they appear to be dysfunctional, having a reduced ability to resorb whale dentin in vitro. Mice are osteosclerotic and hypocalcemic. Enhanced tumor angiogenesis and vascular endothelial growth factor-induced blood vessel growth are observed. This mutant mouse strain represents a model that may be useful in studies related to Glanzmann thrombasthenia.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt exons 1 and 2 of the targeted gene. The construct was transfected into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J for more than 7 generations by the donating laboratory.
|Allele Name||targeted mutation 1, Richard Hynes|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Itgb3tm1Hyn; targeted mutation 1, Richard Hynes|
|Gene Symbol and Name||Itgb3, integrin beta 3|
|Gene Synonym(s)||BDPLT16; CD61; GT; platelet glycoprotein IIIa (GP3A); GPIIIa; GP3A; BDPLT2|
|Strain of Origin||129S2/SvPas|
|Molecular Note||A PGK-neomycin resistance cassette replaced 1.4 kb of sequence including exons I and II. FACS, immunoprecipitation, and immunofluorescence analyses did not detect protein expression in platelets and MEFs from homozygous mutant animals.|
|Mutations Made By|| |
Dr. Richard Hynes, Massachusetts Institute of Technology
When maintained as a live colony, homozygotes or heterozygotes may be bred. On a C57BL/6 background, viability may be compromised and heterozygous females may perform better.
When using the B6.129S2-Itgb3tm1Hyn/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008698 in your Materials and Methods section.
|Heterozygous for Itgb3<tm1Hyn>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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