Homozygous mice for this knock-out show embryonic lethality attributed to fetal hemorrhaging and placental defects. Adult mice are osteosclerotic and hypocalcemic with enhanced tumor angiogenesis and blood vessel growth. 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.
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/6 mice and made homozygous.
|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
Homozygotes are viable and fertile. The expected coat color is black.
When using the B6;129S2-Itgb3tm1Hyn/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004669 in your Materials and Methods section.
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