Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  17
• Reference
  J:114074 Hoover-Plow J, et al., Genetic background determines response to hemostasis and thrombosis. BMC Blood Disord. 2006;6:6
• ID
  MGI:3688285

Genes

Gene	Assay Type
Hmtb3	visible phenotype
Plg	reported elsewhere

Notes

• Experiment
  Twenty-one chromosome substitution strains derived from A/J chromosome donors on a C57BL/6J genetic background were screened for phenotypes related to hemostasis and thrombosis. Animals were subjected to ferric chloride-induced thrombosis formation in the carotid artery and tail bleeding assays. Parental strain A/J exhibits decreased thrombus occlusion time and increased rebleeding time compared to parental strain C57BL/6J.
  
  Chromosome substitution strains C57BL/6J-Chr 5^A/J and C57BL/6J-Chr 17^A/J displayed significantly shorter bleeding times compared to parental strain C57BL/6J. Rebleeding times were significantly longer in chromosome substitution strains C57BL/6J-Chr 11^A/J and C57BL/6J-Chr 17^A/J (P<0.002) compared to background strain C57BL/6J, while C57BL/6J-Chr 5^A/J approached statistical significance (P<0.008). Animals heterosomic for chromosome 5 and chromosome 17 (after crossing back to C57BL/6J) have rebleeding times similar to C57BL/6J, indicating these A/J-derived QTLs have a recessive effect. However, doubly heterosomic animals from crossing (C57BL/6J-Chr 5^A/J x C57BL/6J-Chr 17^A/J)F1 restored the longer rebleeding time phenotype, suggesting the QTLs interact.
  
  Arterial occlusion times were similar between parental strain C57BL/6J and consomicstrains C57BL/6J-Chr 5^A/J and C57BL/6J-Chr 17^A/J, however double heterosomic mice displayed significantly increased arterial occlusion times (P<0.0001) compared to singly heterosomic mice or C57BL/6J.
  
  QTL symbols Hmtb1, Hmtb2, and Hmtb3 were assigned for the hemostasis and thrombosis loci on mouse Chromosome 5, 11, and 17, respectively. The plasminogen activator inhibitor gene Serpine1 (formerly PAI-I) is located on mouse Chromosome 5. Phenotype analysis of B6.129S2-Serpine1^tm1Mlg/Jknockout animals revealed significantly reduced rebleeding times compared to parental strain C57BL/6J. Additionally, Plg (plasminogen) is located at 7.3 cM on mouse Chromosome 17. Phenotypeanalysis of B6.129S2-Plg^tm1Dco/J knockout animals revealed significantly increased bleeding times compared to wild type.