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Hmtb2C57BL/6J
QTL Variant Detail
Nomenclature
QTL variant: Hmtb2C57BL/6J
Name: hemostasis and thrombosis 2; C57BL/6J
MGI ID: MGI:3688290
QTL: Hmtb2  Location: unknown  Genetic Position: Chr11, Syntenic
Variant
origin
Strain of Specimen:  C57BL/6J
Variant
description
Allele Type:    QTL
Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:114074

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 5A/J and C57BL/6J-Chr 17A/J displayed significantly shorter bleeding times compared to parental strain C57BL/6J. Rebleeding times were significantly longer in chromosome substitution strains C57BL/6J-Chr 11A/J and C57BL/6J-Chr 17A/J (P0.002) compared to background strain C57BL/6J, while C57BL/6J-Chr 5 approached statistical significance (P0.008). 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 x C57BL/6J-Chr 17A/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 5A/J and C57BL/6J-Chr 17A/J, however double heterosomic mice displayed significantly increased arterial occlusion times (P0.0001) 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/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-Plgtm1Dco/J knockout animals revealed significantly increased bleeding times compared to wild type.

References
Original:  J:114074 Hoover-Plow J, et al., Genetic background determines response to hemostasis and thrombosis. BMC Blood Disord. 2006;6:6
All:  1 reference(s)

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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
02/16/2021
MGI 6.16
The Jackson Laboratory