B6.D2N-Ahr^d/J

Stock number: 002921
Research areas: Metabolism Research, Research Tools

Description

Mice congenic for aryl hydrocarbon receptor (Ahr) alleles are useful in metabolic research and drug toxicity studies. Sensitivity to carcinogens often differs between the congenic and the recipient strain.

Detailed description

In this congenic strain, the DBA/2-derived d variant of the aryl hydrocarbon receptor gene (Ahr) was introgressed onto the C57BL/6N background. Ahr^d occurs naturally in DBA/2, AKR, 129, SWR, RF, and NZB strains. Mice congenic for Ahr alleles are useful in metabolic research and drug toxicity studies. Sensitivity to carcinogens often differs between the congenic and the recipient strain.

Development

The Ahr^d allele was backcrossed from DBA/2N onto C57BL/6N via a backcross-intercross breeding scheme by Dr. Daniel Nebert. At generation N13 this congenic was then transferred to Dr Alan Poland et al., who then backcrossed the Ahr^d allele onto C57BL/6J, again via a backcross-intercross breeding scheme, and homozygotes at or beyond generation N17 were sent to The Jackson Laboratory in 1997 and maintained by sibling intercross. The d allele found in DBA/2 differs from the b-1 allele found in C57BL by 10 nucleotides, five of which represent amino acid changes.

Allele

Symbol: Ahr^d
Name: d variant
MGI accession ID: MGI:2667196
Generation method: Not Applicable
Marker symbol: Ahr
Marker name: aryl-hydrocarbon receptor
Chromosome: 12
Strain of origin: Not Applicable
Molecular note: This allele encodes a 104 kDa receptor that is stabilized by molybdate and has an affinity for ligand 10-100 fold lower than that of the receptor produced by the C57BL/6J allele. PCR sequencing of cDNA revealed ten nucleotide differences between the coding sequences of the DBA/2J and C57BL/6J receptors. Five of the ten differences would cause amino acid changes. One of these, an apparent T to C transition replaces the opal termination codon in the C57BL/6J allele with an arginine codon in the DBA/2J allele. This change would extend translation of the DBA/2J mRNA by 43 amino acids, accounting for the larger size of the peptide produced by this allele (104 kDa vs 95 kDa for the C57BL/6J allele). A second T to C transition changes a leucine codon in the C57BL/6J allele to a proline codon in the DBA/2J allele, and would likely change secondary structure of the peptide and thus ligand affinity.
General note:

Strain of origin - this allele was found in DBA/2J, AKR/J, 129, SWR, RF, NZB strains