Resistance mechanisms and mutations

Most resistant strains are characterised by one single nucleotide polymorphism (SNP). These SNPs cause the exchange of one amino acid in the VKOR enzyme. These SNPs are dominant, and can be coded either homozygous or heterozygous on the VKORC1 gene, which has only minor impact on the level of resistance. All rat and mouse resistant strains known today, characterised by one or several SNPs, are listed in a table.

Table 1. Polymorphisms on the VKOR enzyme known to be markers of resistance. Not included is the spretus-introgression strain of the house mouse, marked by a combination of polymorphisms (Arg12Trp/Ala26Ser/Ala48Thr/Arg61Leu).


Position of altered amino acid on VKORAmino acid wild-typeAmino acid resistant strainSNP name and abbreviated nameSpecies
120LeucineGlutamineLeu120Gln
L120Q
R. norvegicus
128LeucineGlutamineLeu128Gln
L128Q
R. norvegicus,
M. musculus
128LeucineSerineLeu128Ser
L128S
M. musculus
139TyrosineCysteineTyr139Cys
Y139C
R. norvegicus,
M. musculus,
other species
139TyrosinePhenylalanineTyr139Phe
Y139F
R. norvegicus
139TyrosineSerineTyr139Ser
Y139S
R. norvegicus,
M. musculus