Searching for hemostatic modifier genes affecting the phenotype of mice with very low levels of FVII

FVII^tTA/- mice are heterozygous for the FVII^- null allele and a gene-targeted allele expressing very low levels of FVII. Approximately half the FVII^tTA/- in a mixed C57Bl/6:129x1/SVJ background survive much longer than mice in a C57Bl/6 background, suggesting that genetic background affects the survival of mice expressing very low levels of FVII. A lineage of long-term surviving FVII^tTA/- mice in a predominantly C57Bl/6 background was generated by selecting 16 weeks or older FVII^tTA/- males and breeding them with C57Bl/6 FVII^+/- females. It is postulated that these mice maintain 129x1/SVJ alleles at putative hemostatic modifier loci necessary for the survival of mice expressing very low levels of FVII. A SNP genomic scan was performed on DNA from long-term surviving FVII^tTA/- mice. The scan identified 8 regions enriched for 129x1/SVJ sequences that might contain putative hemostatic modifier genes.