Mouse chromosome 17 candidate modifier genes for thrombosis

Area of Science:

• Genetics and Genomics
• Cardiovascular Biology
• Thrombosis Research

Background:

• Quantitative trait loci (QTLs) for clot stability (Hmtb8, Hmtb9) were identified on mouse chromosome 17.
• These QTL regions are syntenic to human chromosome 18, suggesting conserved genetic regulation of thrombosis.

Purpose of the Study:

• To identify candidate genes within the syntenic QTL regions that may modify clot stability.
• To investigate the role of Emilin2 as a potential modifier of thrombosis susceptibility.

Main Methods:

• Analysis of F2 intercross mice derived from B6 and B6-Chr17(A/J) strains.
• Identification of genes with differential mRNA expression and nonsynonymous single nucleotide polymorphisms (SNPs) in the QTL region.
• Comparative analysis of vessel wall architecture, EMILIN2 protein levels, and clot stability in different mouse strains.

Main Results:

• Seven genes, including Emilin2, showed differential expression between B6 and A/J mice.
• Emilin2 exhibited differential expression and protein levels in plasma, vessel walls, and thrombi.
• B6-Chr17(A/J) mice displayed higher clot stability and Emilin2 mRNA expression, indicating potential epistatic interactions.

Conclusions:

• Emilin2 is a strong candidate gene for modifying clot stability and thrombosis susceptibility.
• Further investigation into Emilin2's role in vascular structure and coagulation is warranted.
• Epistatic interactions may influence clot stability within the identified QTL regions.