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.
Resistance mechanisms and mutations
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 L120Q |
R. norvegicus |
128 | Leucine | Glutamine | Leu128Gln L128Q |
R. norvegicus |
128 | Leucine | Serine | Leu128Ser L128S |
M. musculus |
139 | Tyrosine | Cysteine | Tyr139Cys Y139C |
R. norvegicus, M. musculus, other species |
139 | Tyrosine | Phenylalanine | Tyr139Phe Y139F |
R. norvegicus |
139 | Tyrosine | Serine | Tyr139Ser Y139S |
R. norvegicus, M. musculus |