These integrin beta 3 knock-out 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 studying Glanzmann thrombasthenia and other bleeding disorders.
Jochen Schneider, Washingtion University in St. Louis
Mice that are homozygous for this targeted allele have limited viability, with significant embryonic lethality attributed to fetal hemorrhaging and placental defects. Surviving mice are fertile. No gene product (protein) is detected on the surface of platelets. Pups surviving to three weeks of age may be subject to skin and gastrointestinal tract hemorrhaging. 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 studying Glanzmann thrombasthenia and other bleeding disorders.
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.
This mutation was created by Dr. Richard O. Hynes (Massachusetts Institute of Technology) by designing a targeting vector to replace exons 1 and 2 of the targeted gene with a phosphoglycerate kinase promoter-driven neomycin resistance gene. The construct was transfected into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were bred with C57BL/6 inbred mice, and maintained on a B6;129S2 genetic background prior to arrival at The Jackson Laboratory (as Stock No. 004669). Mice were obtained by Drs. Clay Semenkovich and Jochen G. Schneider (Washington University in St. Louis) and then bred to C57BL/6J inbred mice for at least 8-9 generations using a marker-assisted speed congenic approach prior to arrival at The Jackson Laboratory (as Stock No. 008819). Upon arrival, mice were bred with C57BL/6J for at least one generation to establish the colony.
|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 on this congenic background, these mice may be bred as heterozygotes. On a C57BL/6 background, viability may be compromised and heterozygous females may perform better.
When using the Β3-integrin KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #008819 in your Materials and Methods section.
|Heterozygous or Wild-type 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.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
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