Hmtb3^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Hmtb3^C57BL/6J
• Name: hemostasis and thrombosis 3; C57BL/6J
• MGI ID: MGI:3688295
• QTL: Hmtb3 Location: unknown Genetic Position: Chr17, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL

Phenotypes

Key:

hm	homozygous	ht	heterozygous	tg	involves transgenes	√	phenotype observed
cn	conditional genotype	cx	complex: > 1 genome feature	ot	other: hemizygous, indeterminate,...	N	normal phenotype

Genotype/
Background:

	Allelic Composition	Genetic Background	Cell Line(s)
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cx1	Hmtb1^A/J/Hmtb1^C57BL/6J Hmtb3^A/J/Hmtb3^C57BL/6J	involves: C57BL/6J-Chr 5^A/J * C57BL/6J-Chr 17^A/J

Phenotypes:

Affected Systems	cx1
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homeostasis/metabolism	√
abnormal blood coagulation	√
abnormal thrombosis	√

View phenotypes and curated references for all genotypes (concatenated display).

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 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 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 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/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.

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)