129S-Itgb3^tm1Hyn/J

Stock number: 008700
Research areas: Cardiovascular Research, Developmental Biology Research, Hematological Research, Internal/Organ Research

Description

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.

Detailed description

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.

Development

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 129S4/AvJae for more than 7 generations by the donating laboratory.

Allele

Symbol: Itgb3^tm1Hyn
Name: targeted mutation 1, Richard Hynes
MGI accession ID: MGI:2175913
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Itgb3
Marker name: integrin beta 3
Chromosome: 11
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.