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 VKOR Amino acid wild-type Amino acid resistant strain SNP name and abbreviated name Species
120 Leucine Glutamine Leu120Gln
R. norvegicus
128 Leucine Glutamine Leu128Gln
R. norvegicus
128 Leucine Serine Leu128Ser
M. musculus
139 Tyrosine Cysteine Tyr139Cys
R. norvegicus,
M. musculus,
other species
139 Tyrosine Phenylalanine Tyr139Phe
R. norvegicus
139 Tyrosine Serine Tyr139Ser
R. norvegicus,
M. musculus