GEPHE SUMMARY Print
Gephebase Gene
Entry Status
Published
GepheID
GP00001181
Main curator
Martin
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Rattus norvegicus
Trait State in Taxon B
Rattus norvegicus - France and Belgium
Ancestral State
Data not curated
Taxonomic Status
Taxon A
Common Name
Norway rat
Synonyms
rat; rats; Norway rat; brown rat; Rattus norvegicus8; Rattus norwegicus
Rank
species
Lineage
Show more ... omi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Common Name
Norway rat
Synonyms
rat; rats; Norway rat; brown rat; Rattus norvegicus8; Rattus norwegicus
Rank
species
Lineage
Show more ... omi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
NCBI Taxonomy ID
is Taxon B an Infraspecies?
Yes
Taxon B Description
Rattus norvegicus - France and Belgium
GENOTYPIC CHANGE
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
Y139F
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid - - -
Authors
Lasseur R; Longin-Sauvageon C; Videmann B; Billeret M; Berny P; Benoit E
Abstract
A warfarin-resistant strain and a warfarin-susceptible strain of wild rats (Rattus norvegicus) maintained in enclosures of the National Veterinary School of Lyon (France) were studied to determine the mechanism of the resistance to anticoagulant rodenticides. A low vitamin K epoxide reductase (VKOR) activity has been reported for many resistant rat strains. As recently suggested, mutations in the vitamin K epoxide reductase subunit 1 (VKORC1) gene are the genetic basis of anticoagulant resistance in wild populations of rats from various locations in Europe. Here we report, for our strain, one of the seven described mutations (Tyr139Phe) for VKORC1 in rats. In addition, a low expression of mRNA encoding VKORC1 gene is observed in resistant rats, which could explain their low VKOR activity. We calculated kinetic parameters of VKOR in the warfarin-resistant and warfarin-susceptible rats. The V(max) and the K(m) of the VKOR obtained in resistant rats were lowered by 57 and 77%, respectively, compared to those obtained in susceptible rats. As a consequence, the enzymatic efficiency (V(m)/K(m)) of the VKOR was similar between resistant and susceptible rats. This result could be a good explanation to the observation that no clinical signs of vitamin K deficiency was observed in the warfarin-resistant strain, while a low VKOR activity was found. VKOR activity in warfarin-resistant rats was poorly inhibited by warfarin (K(i) for warfarin is 29 microM and 0.72 microM for resistant and susceptible rats, respectively).

(c) 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:379-385, 2005
RELATED GEPHE
Related Haplotypes
7
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