B6.129-Tyro3^tm1Grl/J

Stock number: 007937
Research areas: Cardiovascular Research, Hematological Research

Description

Mice that are homozygous for this mutation may be useful in studies of thrombosis and platelet aggregation. Thrombin-treated mutants exhibit reduced pathological thrombosis and impaired platelet aggregation.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of brain lysate. Homozygotes exhibit decreased sensitivity to induced pathological thrombosis resulting in reduced fatal pulmonary embolism (25% of wild-type). Platelet aggregation and clot retraction after thrombin treatment is impaired. Platelet signaling and secretion is also defective. Activity induced seizures can occur in mutant mice over the age of seven months. This mutant mouse strain may be useful in studies of thrombosis and platelet aggregation.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 9 and part of exon 10. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting animals were crossed to C57BL/6 mice and then made homozygous. The mice were then backcrossed to C57BL/6 for five generations.

Allele

Symbol: Tyro3^tm1Grl
Name: targeted mutation 1, Greg Lemke
MGI accession ID: MGI:2387762
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tyro3
Marker name: TYRO3 protein tyrosine kinase 3
Chromosome: 2
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A neomycin selection cassette replaced sequences containing exon 9 and part of exon 10. Western blot analysis on brain lysates derived from homozygous mice confirmed that no detectable protein was produced from this allele.