Strain Name:

B6.Cg-Cyp1a2/Cyp1a1tm2Dwn Ahrd Tg(CYP1A1,CYP1A2)1Dwn/DwnJ

Stock Number:

008599

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Availability:

Cryopreserved - Ready for recovery

Common Names: "humanized" hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahr<d> mutant mice;    
These "humanized" hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahrd mice carry the human CYP1A1 and CYP1A2 genes in the absence of functional mouse Cyp1a1 and Cyp1a2 orthologs, and also mimic the human poor-affinity aryl hydrocarbon receptor (AHR) by carrying the poor-affinity Ahrd allele derived from DBA/2J mice. These may be useful in drug or carcinogen metabolism research; specifically as a model for human risk assessment studies involving drug or environmental toxicants that may be substrates for the aryl hydrocarbon receptor (AHR) or cytochrome P450 family 1 members.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Spontaneous Mutation; Targeted Mutation; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN6+F4p
Generation Definitions
 
Donating Investigator Daniel W Nebert,   University of Cincinnati Medical Center

Description
These "humanized" hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahrd mice carry the human CYP1A1 and CYP1A2 genes in the absence of functional mouse Cyp1a1 and Cyp1a2 orthologs, and also mimic the human poor-affinity aryl hydrocarbon receptor (AHR) by carrying the poor-affinity Ahrd allele derived from DBA/2J mice (rather than the high-affinity Ahrb1 allele normally present on a C57BL/6J genetic background); all on a C57BL/6J (reported >99.8%) genetic background.

Mice homozygous for the Cyp1a2/Cyp1a1 targeted allele [Cyp1a1/1a2(-/-)], homozygous for the Ahrd allele, and carrying the hCYP1A1_1A2 transgene are viable and fertile with normal lifespan. As the Cyp1a2/Cyp1a1(-) targeted allele lacks the coding regions of both Cyp1a1 and Cyp1a2 genes, no mouse CYP1A1 or CYP1A2 mRNA expression is observed in liver, lung or kidney. Transgene expression of the orthologous human genes is observed in the same tissues. Because expression of the hCYP1A1_1A2 transgene is controlled by the mouse AHR, the low-affinity Ahrd allele results in diminished CYP1A responses following exposure to AHR inducers (such as dioxin) when compared to hCYP1A1_1A2_Cyp1a1/1a2(-/-) mice harboring a high-affinity Ahr allele. These humanized hCYP1A1_1A2_Cyp1a2/Cyp1a1(-/-)_Ahrd mice may be useful in drug or carcinogen metabolism research; specifically as a model for human risk assessment studies involving drug or environmental toxicants that may be substrates for the aryl hydrocarbon receptor (AHR) or cytochrome P450 family 1 members.

Development
These "humanized" hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahrd mutant mice were generated in the laboratory of Dr. Daniel W. Nebert (University of Cincinnati Medical Center). These mice were generated by breeding hCYP1A1_1A2_Cyp1a1/1a2(-/-) mice (see Stock No. 007580, but reportedly maintained on a >99.8% C57BL/6J genetic background) to B6.D2-Ahrd mice (Stock No. 002921). The resulting mice were subsequently bred with B6.D2-Ahrd mice for at least 2 generations to fix the Ahrd allele to homozygosity. Mice homozygous for the Cyp1a1/1a2 mutation, homozygous for the Ahrd allele, and carrying the hCYP1A1_1A2 transgene were sent to The Jackson Laboratory. Upon arrival, mice were bred with B6.D2-Ahrd mice (Stock No. 002921) for at least one generation to establish this colony.

Upon rederivation of these mice at The Jackson Laboratory, we will perform a genetic background analysis using a single nucleotide polymorphism (SNP) analysis. The results of this analysis have not yet been completed (December 2008).

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Ahrd allele
000690   129P3/J
000648   AKR/J
002921   B6.D2N-Ahrd/J
000652   BDP/J
000928   CAST/EiJ
000671   DBA/2J
000674   I/LnJ
000675   LG/J
000676   LP/J
000684   NZB/BlNJ
000726   RBF/DnJ
000682   RF/J
000686   SJL/J
000688   ST/bJ
000689   SWR/J
000693   WC/ReJ KitlSl/J
000933   YBR/EiJ
View Strains carrying   Ahrd     (17 strains)

Strains carrying   Cyp1a2/Cyp1a1tm2Dwn allele
007580   STOCK Cyp1a2/Cyp1a1tm2Dwn Tg(CYP1A1,CYP1A2)1Dwn/J
View Strains carrying   Cyp1a2/Cyp1a1tm2Dwn     (1 strain)

Strains carrying   Tg(CYP1A1,CYP1A2)1Dwn allele
007580   STOCK Cyp1a2/Cyp1a1tm2Dwn Tg(CYP1A1,CYP1A2)1Dwn/J
View Strains carrying   Tg(CYP1A1,CYP1A2)1Dwn     (1 strain)

Strains carrying other alleles of Ahr
000645   A/HeJ
000646   A/J
002920   B6(D2N).Spretus-Ahrb-3/J
002831   B6.129-Ahrtm1Bra/J
000130   B6.C-H17c/(HW14)ByJ
000136   B6.C-H34c/(HW22)ByJ
000370   B6.C-H38c/(HW119)ByJ
002727   B6;129-Ahrtm1Bra/J
001026   BALB/cByJ
000653   BUB/BnJ
000659   C3H/HeJ
000663   C57BL/6By
001139   C57BL/6ByJ
000664   C57BL/6J
000662   C57BLKS/J
000667   C57BR/cdJ
000668   C57L/J
000669   C58/J
000926   CAROLI/EiJ
000656   CBA/J
000657   CE/J
000351   CXB1/ByJ
000352   CXB2/ByJ
000353   CXB3/ByJ
000354   CXB4/ByJ
000355   CXB5/ByJ
000356   CXB6/ByJ
000357   CXB7/ByJ
002937   D2.B6-Ahrb-1/J
000673   HRS/J
000677   MA/MyJ
000550   MOLF/EiJ
000679   P/J
000930   PERA/EiJ
000644   SEA/GnJ
000280   SF/CamEiJ
001146   SPRET/EiJ
006203   STOCK Ahrtm3.1Bra/J
View Strains carrying other alleles of Ahr     (38 strains)

Strains carrying other alleles of CYP1A1
003538   B6.Cg-Tg(APOC2)2Bres/J
002925   B6;CBA-Tg(APOC2)2Bres/J
View Strains carrying other alleles of CYP1A1     (2 strains)

Strains carrying other alleles of Cyp1a1
012636   B6.129P2-Cyp1a1tm1Dwn/Mmjax
View Strains carrying other alleles of Cyp1a1     (1 strain)

Strains carrying other alleles of Cyp1a2
002909   129-Cyp1a2tm1Gonz/J
View Strains carrying other alleles of Cyp1a2     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Cytochrome P450, Subfamily I, Polypeptide 2; CYP1A2   (CYP1A2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Cyp1a2/Cyp1a1tm2Dwn/Cyp1a2/Cyp1a1tm2Dwn Tg(CYP1A1,CYP1A2)1Dwn/Tg(CYP1A1,CYP1A2)1Dwn

        B6.Cg-Cyp1a2/Cyp1a1tm2Dwn Tg(CYP1A1,CYP1A2)1Dwn
  • liver/biliary system phenotype
  • enlarged liver
    • after oral treatment with 125 mg/kg/day of benzo[a]pyrene BaP, mice show increased liver size   (MGI Ref ID J:122409)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Cancer Research
Toxicology

Cell Biology Research
Transcriptional Regulation

Research Tools
Cancer Research
Cell Biology Research
Metabolism Research
Toxicology Research
      drug metabolism
      drug/compound testing

Ahrd related

Metabolism Research

Research Tools
Toxicology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ahrd
Allele Name d variant
Allele Type Not Applicable
Common Name(s) Ahd; Ahk; AhRd; Ahhn; ah; in;
Gene Symbol and Name Ahr, aryl-hydrocarbon receptor
Chromosome 12
Gene Common Name(s) Ah; Ahh; Ahre; In; aromatic hydrocarbon responsiveness; aryl hydrocarbon hydroxylase; bHLHe76; dioxin receptor; inflammatory reactivity;
General Note Compared with Ahrd/Ahrd mice, Ahrb/Ahrb individuals have a high inflammatory response to cutaneous application of dimethylbenzanthracene; a high susceptibility to methylcholanthrene- and benzopyrene-induced subcutaneous sarcomas and methylcholanthrene-induced lung tumors; an increased resistance to zoxazolamine-induced paralysis, lindane toxicity, and benzo[a]pyrene-induced aplastic anemia and leukemia; a high susceptibility to acetaminophen-induced hepatic necrosis and cataract formation; and an increased susceptibility to polycyclic hydrocarbon-induced birth defects, stillbirths, resorptions, decreased body weight, ovarian primordial oocyte depletion, and spermatozoal aberrations (J:5822). The Ahrballele is associated with increases in numerous metabolites of chemical carcinogens binding to DNA nucleotides (J:12156). The effectiveness of several mutagens for Salmonella in vitro is enhanced by presence of a liver fraction from Ahrb/Ahrb> mice treated with polycyclic hydrocarbons, but not from similarly treated Ahrd/Ahr mice (J:5564). In contrast, oral doses of benzopyrene cause a high rate of leukemia in Ahrd/Ahrd but not in Ahrd/Ahrd mice, probably because the carcinogenic metabolites produced in responsive Ahrb/Ahrd mice are rapidly degraded in the intestine and excreted in the feces (J:6074).

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

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. [MGI Ref ID J:15153] [MGI Ref ID J:17460] [MGI Ref ID J:22144]
 
Allele Symbol Cyp1a2/Cyp1a1tm2Dwn
Allele Name targeted mutation 2, Daniel W Nebert
Allele Type Targeted (knock-out)
Common Name(s) Cyp1a1/1a2-;
Strain of Origin129P2/OlaHsd and 129S6/SvEvTac
Gene Symbol and Name Cyp1a1, cytochrome P450, family 1, subfamily a, polypeptide 1
Chromosome 9
Gene Common Name(s) AHH; AHRR; CP11; CYP1; Cyp45c; Cypc45c; P-450MC; P1-450; P450-1; P450-C; P450DX; cytochrome P450 subfamily I, polypeptide 1;
Molecular Note The Cyp1a2(t) targeted allele (J:122409) was generated using a targeting vector designed to insert a loxP-flanked PGK-NEO cassette 350 bp downstream of the endogenous stop codon (about 60 bp 3' of exon 7). The construct was electroporated into 129S6/SvEvTac-derived embryonic stem (ES) cells which were microinjection into C57BL/6 blastocysts. The chimeras were bred with C57BL/6 to generate Cyp1a2(t) mutant mice. To create the Cyp1a1 targeted allele (J:59398), a targeting vector was designed to insert a loxP-flanked hypoxanthine phosphoribosyltransferase (HPRT) minigene in intron 1 and a loxP site downstream of the termination codon in exon 7. Following electroporation into E14TG2a (HPRT-) ES cells and ES cell microinjection into the blastocoele cavity of C57BL/6J embryos, chimeric males were bred with C57BL/6J females. As described in J:86748, these Cyp1a1(t) mutant mice were then bred to a Cre-deleter strain (CAGGS-CRE, mixed C57BL/6J and FVB/NJ genetic background). The resulting transgenic mice found tobe heterozygous for the floxed null Cyp1a1(-) allele (containing only exon 1, a portion of intron 1, and one remaining loxP site in the 3' UTR) were bred to mice heterozygous for the Cyp1a2(t) allele (as described in J:122409). Mutant mice (Cyp1a2(t), Cyp1a1(-), CAGGS-CRE) were bred to C57BL/6. Because of the close genomic position of these two genes, offspring having undergone Cre recombinase-mediated interchromosomal recombination between the loxP sites 3' beyond the stop codons of the Cyp1a2 and Cyp1a1 genes could be selected. Such mice were backcrossed to C57BL/6 for 10 generations (while selecting against the Cre-deleter transgene) to generate Cyp1a1/1a2 mutant mice. [MGI Ref ID J:122409] [MGI Ref ID J:59398] [MGI Ref ID J:86748]
 
Gene Symbol and Name Cyp1a2, cytochrome P450, family 1, subfamily a, polypeptide 2
Chromosome 9
Gene Common Name(s) CP12; CYPD45; P-450d; P3-450; P450(PA); P450-3; RATCYPD45; aromatic compound inducible;
 
Allele Symbol Tg(CYP1A1,CYP1A2)1Dwn
Allele Name transgene insertion 1, Daniel W Nebert
Allele Type Transgenic (random, expressed)
Common Name(s) hCYP1A1_1A2, BAC-H;
Strain of Origin(C57BL/6J x DBA/2J)F1
Expressed Gene CYP1A1, cytochrome P450, family 1, subfamily A, polypeptide 1, human
Expressed Gene CYP1A2, cytochrome P450, family 1, subfamily A, polypeptide 2, human
Promoter CYP1A1, cytochrome P450, family 1, subfamily A, polypeptide 1, human
Promoter CYP1A2, cytochrome P450, family 1, subfamily A, polypeptide 2, human
Molecular Note To create "humanized" CYP1A1 and CYP1A2 transgenic mice (hCYP1A1_1A2), a single copy of the 180-kb human CYP1A1_CYP1A2 locus-containing BAC-H (BAC Human CTB clone 31H21: including the 23.3 kb spacer region, 90 kb of CYP1A2 3'-flanking region and 53 kb ofCYP1A1 3' flanking region) was microinjected into (C57BL/6J x DBA/2J)F1 oocytes. Founder mice having a single copy of BAC-H were identified and then backcrossed for 10 generations to C57BL/6 mice. [MGI Ref ID J:96716]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Cyp1a2/Cyp1a1tm2Dwn, Melt Curve Analysis
Cyp1a2/Cyp1a1tm2Dwn, Standard PCR
Tg(Cyp1a1), Melt Curve Analysis
Tg(Cyp1a1), Standard PCR
Tg(Cyp1a2), Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Shi Z; Chen Y; Dong H; Amos-Kroohs RM; Nebert DW. 2008. Generation of a 'humanized' hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahrd mouse line harboring the poor-affinity aryl hydrocarbon receptor. Biochem Biophys Res Commun 376(4):775-80. [PubMed: 18814841]  [MGI Ref ID J:141523]

Additional References

Ahrd related

Benedict WF; Considine N; Nebert DW. 1973. Genetic differences in aryl hydrocarbon hydroxylase induction and benzo(a)pyrene-produced tumorigenesis in the mouse. Mol Pharmacol 9(2):266-77. [PubMed: 4123113]  [MGI Ref ID J:84312]

Boobis AR; Nebert DW. 1976. Genetic differences in the metabolism of carcinogens and in the binding of benzo (a) pyrene metabolites to DNA. Adv Enzyme Regul 15:339-62. [PubMed: 1030186]  [MGI Ref ID J:12156]

Castro DJ; Lohr CV; Fischer KA; Pereira CB; Williams DE. 2008. Lymphoma and lung cancer in offspring born to pregnant mice dosed with dibenzo[a,l]pyrene: the importance of in utero vs. lactational exposure. Toxicol Appl Pharmacol 233(3):454-8. [PubMed: 18848954]  [MGI Ref ID J:143604]

Chang C; Smith DR; Prasad VS; Sidman CL; Nebert DW; Puga A. 1993. Ten nucleotide differences, five of which cause amino acid changes, are associated with the Ah receptor locus polymorphism of C57BL/6 and DBA/2 mice. Pharmacogenetics 3(6):312-21. [PubMed: 8148872]  [MGI Ref ID J:17460]

Curran CP; Miller KA; Dalton TP; Vorhees CV; Miller ML; Shertzer HG; Nebert DW. 2006. Genetic differences in lethality of newborn mice treated in utero with coplanar versus non-coplanar hexabromobiphenyl. Toxicol Sci 89(2):454-64. [PubMed: 16291824]  [MGI Ref ID J:113285]

Felton JS; Nebert DW. 1975. Mutagenesis of certain activated carcinogens in vitro associated with genetically mediated increases in monooxygenase activity and cytochrome P 1-450. J Biol Chem 250(17):6769-78. [PubMed: 808546]  [MGI Ref ID J:5564]

Gielen JE; Goujon FM; Nebert DW. 1972. Genetic regulation of aryl hydrocarbon hydroxylase induction. II. Simple Mendelian expression in mouse tissues in vivo. J Biol Chem 247(4):1125-37. [PubMed: 4110756]  [MGI Ref ID J:84250]

Goujon FM; Nebert DW; Gielen JE. 1972. Genetic expression of aryl hydrocarbon hydroxylase induction. IV. Interaction of various compounds with different forms of cytochrome P-450 and the effect on benzo(a)pyrene metabolism in vitro. Mol Pharmacol 8(6):667-80. [PubMed: 4118365]  [MGI Ref ID J:84252]

Harper PA; Golas CL; Okey AB. 1991. Ah receptor in mice genetically nonresponsive for cytochrome P4501A1 induction: cytosolic Ah receptor, transformation to the nuclear binding state, and induction of aryl hydrocarbon hydroxylase by halogenated and nonhalogenated aromatic hydrocarbons in embryonic tissues and cells. Mol Pharmacol 40(5):818-26. [PubMed: 1658612]  [MGI Ref ID J:2134]

Kerley-Hamilton JS; Trask HW; Ridley CJ; Dufour E; Lesseur C; Ringelberg CS; Moodie KL; Shipman SL; Korc M; Gui J; Shworak NW; Tomlinson CR. 2012. Inherent and benzo[a]pyrene-induced differential aryl hydrocarbon receptor signaling greatly affects life span, atherosclerosis, cardiac gene expression, and body and heart growth in mice. Toxicol Sci 126(2):391-404. [PubMed: 22228805]  [MGI Ref ID J:183715]

Kouri RE; Rude TH; Joglekar R; Dansette PM; Jerina DM; Atlas SA; Owens IS; Nebert DW. 1978. 2,3,7,8-tetrachlorodibenzo-p-dioxin as cocarcinogen causing 3-methylcholanthrene-initiated subcutaneous tumors in mice genetically 'nonresponsive' at Ah locus. Cancer Res 38(9):2777-83. [PubMed: 679184]  [MGI Ref ID J:84318]

Levova K; Moserova M; Nebert DW; Phillips DH; Frei E; Schmeiser HH; Arlt VM; Stiborova M. 2012. NAD(P)H:quinone oxidoreductase expression in Cyp1a-knockout and CYP1A-humanized mouse lines and its effect on bioactivation of the carcinogen aristolochic acid I. Toxicol Appl Pharmacol 265(3):360-7. [PubMed: 22982977]  [MGI Ref ID J:192865]

Lew BJ; Manickam R; Lawrence BP. 2011. Activation of the aryl hydrocarbon receptor during pregnancy in the mouse alters mammary development through direct effects on stromal and epithelial tissues. Biol Reprod 84(6):1094-102. [PubMed: 21270426]  [MGI Ref ID J:173706]

Moriguchi T; Motohashi H; Hosoya T; Nakajima O; Takahashi S; Ohsako S; Aoki Y; Nishimura N; Tohyama C; Fujii-Kuriyama Y; Yamamoto M. 2003. Distinct response to dioxin in an arylhydrocarbon receptor (AHR)-humanized mouse. Proc Natl Acad Sci U S A 100(10):5652-7. [PubMed: 12730383]  [MGI Ref ID J:132380]

Nebert DW; Atlas SA; Guenthner TM; Kouri RE. 1978. The Ah locus: genetic regulation of the enzymes which metabolize polycyclic hydrocarbons and the risk of cancer. In: Polycyclic Hydrocarbons and Cancer: Chemistry, Molecular Biology and Environment. Academic Press, New York.  [MGI Ref ID J:30693]

Nebert DW; Considine N; Owens IS. 1973. Genetic expression of aryl hydrocarbon hydroxylase induction. VI. Control of other aromatic hydrocarbon-inducible mono-oxygenase activities at or near the same genetic locus. Arch Biochem Biophys 157(1):148-59. [PubMed: 4716952]  [MGI Ref ID J:84313]

Nebert DW; Gelboin HV. 1969. The in vivo and in vitro induction of aryl hydrocarbon hydroxylase in mammalian cells of different species, tissues, strains, and developmental and hormonal states. Arch Biochem Biophys 134(1):76-89. [PubMed: 4981257]  [MGI Ref ID J:84248]

Nebert DW; Gielen JE. 1972. Genetic regulation of aryl hydrocarbon hydroxylase induction in the mouse. Fed Proc 31(4):1315-25. [PubMed: 4114109]  [MGI Ref ID J:5282]

Nebert DW; Gielen JE; Goujon FM. 1972. Genetic expression of aryl hydrocarbon hydroxylase induction. 3. Changes in the binding of n-octylamine to cytochrome P-450. Mol Pharmacol 8(6):651-66. [PubMed: 4118364]  [MGI Ref ID J:84251]

Nebert DW; Goujon FM; Gielen JE. 1972. Aryl hydrocarbon hydroxylase induction by polycyclic hydrocarbons: simple autosomal dominant trait in the mouse. Nat New Biol 236(65):107-10. [PubMed: 4502804]  [MGI Ref ID J:84249]

Nebert DW; Jensen NM. 1979. Benzo[a]pyrene-initiated leukemia in mice. Association with allelic differences at the Ah locus. Biochem Pharmacol 28(1):149-51. [PubMed: 758905]  [MGI Ref ID J:6074]

Nebert DW; Jensen NM; Shinozuka H; Kunz HW; Gill TJ 3rd. 1982. The Ah phenotype. Survey of forty-eight rat strains and twenty inbred mouse strains. Genetics 100(1):79-87. [PubMed: 7095422]  [MGI Ref ID J:6809]

Nebert DW; Kon H. 1973. Genetic regulation of aryl hydrocarbon hydroxylase induction. V. Specific changes in spin state of cytochrome P 450 from genetically responsive animals. J Biol Chem 248(1):169-78. [PubMed: 4348203]  [MGI Ref ID J:84311]

Nebert DW; Robinson JR; Niwa A; Kumaki K; Poland AP. 1975. Genetic expression of aryl hydrocarbon hydroxylase activity in the mouse. J Cell Physiol 85(2 Pt 2 Suppl 1):393-414. [PubMed: 1091656]  [MGI Ref ID J:84317]

Niwa A; Kumaki K; Nebert DW; Poland AP. 1975. Genetic expression of aryl hydrocarbon hydroxylase activity in the mouse. Distinction between the 'responsive' homozygote and heterozygote at the Ah locus. Arch Biochem Biophys 166(2):559-64. [PubMed: 1119809]  [MGI Ref ID J:84316]

Oesch F; Morris N; Daly JW. 1973. Genetic expression of the induction of epoxide hydrase and aryl hydrocarbon hydroxylase activities in the mouse by phenobarbital or 3-methylcholanthrene. Mol Pharmacol 9(5):629-6. [PubMed: 4788156]  [MGI Ref ID J:25852]

Okey AB; Vella LM; Harper PA. 1989. Detection and characterization of a low affinity form of cytosolic Ah receptor in livers of mice nonresponsive to induction of cytochrome P1-450 by 3-methylcholanthrene. Mol Pharmacol 35(6):823-30. [PubMed: 2543914]  [MGI Ref ID J:27899]

Poel WE; Stanton D; Peters E; Wade HO. 1958. Comparative susceptibilities of seven inbred strains of mice to qualified applications of 3, 4-benzpyrene Proc Am Assoc Cancer Res 2:335.  [MGI Ref ID J:84245]

Poland A; Bradfield C. 1992. A brief review of the Ah locus. Tohoku J Exp Med 168(2):83-7. [PubMed: 1339107]  [MGI Ref ID J:12546]

Poland A; Glover E. 1990. Characterization and strain distribution pattern of the murine Ah receptor specified by the Ahd and Ahb-3 alleles. Mol Pharmacol 38(3):306-12. [PubMed: 2169579]  [MGI Ref ID J:34840]

Poland A; Glover E; Kende AS. 1976. Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase. J Biol Chem 251(16):4936-46. [PubMed: 956169]  [MGI Ref ID J:84247]

Poland A; Glover E; Taylor BA. 1987. The murine Ah locus: a new allele and mapping to chromosome 12. Mol Pharmacol 32(4):471-8. [PubMed: 2823093]  [MGI Ref ID J:8895]

Poland A; Palen D; Glover E. 1994. Analysis of the four alleles of the murine aryl hydrocarbon receptor. Mol Pharmacol 46(5):915-21. [PubMed: 7969080]  [MGI Ref ID J:22144]

Poland A; Teitelbaum P; Glover E; Kende A. 1989. Stimulation of in vivo hepatic uptake and in vitro hepatic binding of [125I]2-lodo-3,7,8-trichlorodibenzo-p-dioxin by the administration of agonist for the Ah receptor. Mol Pharmacol 36(1):121-7. [PubMed: 2546046]  [MGI Ref ID J:126377]

Poland AP; Glover E; Robinson JR; Nebert DW. 1974. Genetic expression of aryl hydrocarbon hydroxylase activity. Induction of monooxygenase activities and cytochrome P1-450 formation by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice genetically 'nonresponsive' to other aromatic hydrocarbons. J Biol Chem 249(17):5599-606. [PubMed: 4370044]  [MGI Ref ID J:84314]

Quintana FJ; Basso AS; Iglesias AH; Korn T; Farez MF; Bettelli E; Caccamo M; Oukka M; Weiner HL. 2008. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453(7191):65-71. [PubMed: 18362915]  [MGI Ref ID J:136052]

Robinson JR; Considine N; Nebert DW. 1974. Genetic expression of aryl hydrocarbon hydroxylase induction. Evidence for the involvement of other genetic loci. J Biol Chem 249(18):5851-9. [PubMed: 4413562]  [MGI Ref ID J:84315]

Schmid FA; Demetriades MS; Schabel FM 3rd; Tarnowski GS. 1967. Toxicity of several cancerigenic polycyclic hydrocarbons and other agents in AKR and C57BL-6 mice. Cancer Res 27(3):563-7. [PubMed: 6021514]  [MGI Ref ID J:84246]

Schmid FA; Elmer I; Tarnowski GS. 1969. Genetic determination of differential inflammatory reactivity and subcutaneous tumor susceptibility of AKR-J and C57BL-6J mice to 7,12-dimethylbenz- [a]anthracene. Cancer Res 29(8):1585-9. [PubMed: 5807232]  [MGI Ref ID J:34134]

Schmid FA; Pena RC; Robinson W; Tarnowski GS. 1967. Toxicity of intraperitoneal injections of 7, 12-dimethylbenz[a]anthracene in inbred mice. Cancer Res 27(3):558-62. [PubMed: 6021513]  [MGI Ref ID J:26440]

Schmidt JV; Carver LA; Bradfield CA. 1993. Molecular characterization of the murine Ahr gene. Organization, promoter analysis, and chromosomal assignment. J Biol Chem 268(29):22203-9. [PubMed: 8408082]  [MGI Ref ID J:15153]

Shivanna B; Zhang W; Jiang W; Welty SE; Couroucli XI; Wang L; Moorthy B. 2013. Functional deficiency of aryl hydrocarbon receptor augments oxygen toxicity-induced alveolar simplification in newborn mice. Toxicol Appl Pharmacol 267(3):209-17. [PubMed: 23337360]  [MGI Ref ID J:193493]

Simonian PL; Wehrmann F; Roark CL; Born WK; O'Brien RL; Fontenot AP. 2010. gammadelta T cells protect against lung fibrosis via IL-22. J Exp Med 207(10):2239-53. [PubMed: 20855496]  [MGI Ref ID J:165803]

Smith AG; Clothier B; Robinson S; Scullion MJ; Carthew P; Edwards R; Luo J; Lim CK; Toledano M. 1998. Interaction between iron metabolism and 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice with variants of the Ahr gene: a hepatic oxidative mechanism. Mol Pharmacol 53(1):52-61. [PubMed: 9443932]  [MGI Ref ID J:45850]

Stiborova M; Levova K; Barta F; Shi Z; Frei E; Schmeiser HH; Nebert DW; Phillips DH; Arlt VM. 2012. Bioactivation versus detoxication of the urothelial carcinogen aristolochic acid I by human cytochrome P450 1A1 and 1A2. Toxicol Sci 125(2):345-58. [PubMed: 22086975]  [MGI Ref ID J:183662]

Tanos R; Murray IA; Smith PB; Patterson A; Perdew GH. 2012. Role of the ah receptor in homeostatic control of Fatty Acid synthesis in the liver. Toxicol Sci 129(2):372-9. [PubMed: 22696238]  [MGI Ref ID J:188164]

Taylor BA. 1971. Strain distribution and linkage tests of 7,12-dimethylbenzanthracene (DMBA) inflammatory response in mice. Life Sci I 10(19):1127-34. [PubMed: 5132702]  [MGI Ref ID J:5244]

Thomas PE; Hutton JJ; Taylor BA. 1973. Genetic relationship between aryl hydrocarbon hydroxylase inducibility and chemical carcinogen induced skin ulceration in mice. Genetics 74(4):655-9. [PubMed: 4750810]  [MGI Ref ID J:5387]

Thomas PE; Kouri RE; Hutton JJ. 1972. The genetics of aryl hydrocarbon hydroxylase induction in mice: a single gene difference between C57BL-6J and DBA-2J. Biochem Genet 6(2):157-68. [PubMed: 4666754]  [MGI Ref ID J:31977]

Thorgeirsson SS; Nebert DW. 1977. The Ah locus and the metabolism of chemical carcinogens and other foreign compounds. Adv Cancer Res 25:149-93. [PubMed: 405846]  [MGI Ref ID J:5822]

Walisser JA; Bunger MK; Glover E; Bradfield CA. 2004. Gestational exposure of Ahr and Arnt hypomorphs to dioxin rescues vascular development. Proc Natl Acad Sci U S A 101(47):16677-82. [PubMed: 15545609]  [MGI Ref ID J:94465]

Yeager RL; Reisman SA; Aleksunes LM; Klaassen CD. 2009. Introducing the 'TCDD-inducible AhR-Nrf2 gene battery'. Toxicol Sci 111(2):238-46. [PubMed: 19474220]  [MGI Ref ID J:154083]

Yu Z; Mahadevan B; Lohr CV; Fischer KA; Louderback MA; Krueger SK; Pereira CB; Albershardt DJ; Baird WM; Bailey GS; Williams DE. 2006. Indole-3-carbinol in the maternal diet provides chemoprotection for the fetus against transplacental carcinogenesis by the polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene. Carcinogenesis 27(10):2116-23. [PubMed: 16704990]  [MGI Ref ID J:113356]

Zhou Y; Tung HY; Tsai YM; Hsu SC; Chang HW; Kawasaki H; Tseng HC; Plunkett B; Gao P; Hung CH; Vonakis BM; Huang SK. 2013. Aryl hydrocarbon receptor controls murine mast cell homeostasis. Blood 121(16):3195-204. [PubMed: 23462117]  [MGI Ref ID J:197552]

Cyp1a2/Cyp1a1tm2Dwn related

Cheung C; Loy S; Li GX; Liu AB; Yang CS. 2011. Rapid induction of colon carcinogenesis in CYP1A-humanized mice by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate. Carcinogenesis 32(2):233-9. [PubMed: 21081470]  [MGI Ref ID J:168018]

Dalton TP; Dieter MZ; Matlib RS; Childs NL; Shertzer HG; Genter MB; Nebert DW. 2000. Targeted knockout of Cyp1a1 gene does not alter hepatic constitutive expression of other genes in the mouse [Ah] battery. Biochem Biophys Res Commun 267(1):184-9. [PubMed: 10623596]  [MGI Ref ID J:59398]

Divanovic S; Dalli J; Jorge-Nebert LF; Flick LM; Galvez-Peralta M; Boespflug ND; Stankiewicz TE; Fitzgerald JM; Somarathna M; Karp CL; Serhan CN; Nebert DW. 2013. Contributions of the three CYP1 monooxygenases to pro-inflammatory and inflammation-resolution lipid mediator pathways. J Immunol 191(6):3347-57. [PubMed: 23956430]  [MGI Ref ID J:205875]

Dragin N; Shi Z; Madan R; Karp CL; Sartor MA; Chen C; Gonzalez FJ; Nebert DW. 2008. Phenotype of the Cyp1a1/1a2/1b1-/- triple-knockout mouse. Mol Pharmacol 73(6):1844-56. [PubMed: 18372398]  [MGI Ref ID J:153792]

Dragin N; Uno S; Wang B; Dalton TP; Nebert DW. 2007. Generation of 'humanized' hCYP1A1_1A2_Cyp1a1/1a2(-/-) mouse line. Biochem Biophys Res Commun 359(3):635-42. [PubMed: 17560947]  [MGI Ref ID J:122409]

Iqbal J; Sun L; Cao J; Yuen T; Lu P; Bab I; Leu NA; Srinivasan S; Wagage S; Hunter CA; Nebert DW; Zaidi M; Avadhani NG. 2013. Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of Cyp1 enzymes. Proc Natl Acad Sci U S A 110(27):11115-20. [PubMed: 23776235]  [MGI Ref ID J:198711]

Levova K; Moserova M; Nebert DW; Phillips DH; Frei E; Schmeiser HH; Arlt VM; Stiborova M. 2012. NAD(P)H:quinone oxidoreductase expression in Cyp1a-knockout and CYP1A-humanized mouse lines and its effect on bioactivation of the carcinogen aristolochic acid I. Toxicol Appl Pharmacol 265(3):360-7. [PubMed: 22982977]  [MGI Ref ID J:192865]

Stiborova M; Levova K; Barta F; Shi Z; Frei E; Schmeiser HH; Nebert DW; Phillips DH; Arlt VM. 2012. Bioactivation versus detoxication of the urothelial carcinogen aristolochic acid I by human cytochrome P450 1A1 and 1A2. Toxicol Sci 125(2):345-58. [PubMed: 22086975]  [MGI Ref ID J:183662]

Uno S; Wang B; Shertzer HG; Nebert DW; Dalton TP. 2003. Balancer-Cre transgenic mouse germ cells direct the incomplete resolution of a tri-loxP-targeted Cyp1a1 allele, producing a conditional knockout allele. Biochem Biophys Res Commun 312(2):494-9. [PubMed: 14637164]  [MGI Ref ID J:86748]

Tg(CYP1A1,CYP1A2)1Dwn related

Cheung C; Loy S; Li GX; Liu AB; Yang CS. 2011. Rapid induction of colon carcinogenesis in CYP1A-humanized mice by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate. Carcinogenesis 32(2):233-9. [PubMed: 21081470]  [MGI Ref ID J:168018]

Dragin N; Uno S; Wang B; Dalton TP; Nebert DW. 2007. Generation of 'humanized' hCYP1A1_1A2_Cyp1a1/1a2(-/-) mouse line. Biochem Biophys Res Commun 359(3):635-42. [PubMed: 17560947]  [MGI Ref ID J:122409]

Jiang Z; Dalton TP; Jin L; Wang B; Tsuneoka Y; Shertzer HG; Deka R; Nebert DW. 2005. Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus. Hum Mutat 25(2):196-206. [PubMed: 15643613]  [MGI Ref ID J:96716]

Levova K; Moserova M; Nebert DW; Phillips DH; Frei E; Schmeiser HH; Arlt VM; Stiborova M. 2012. NAD(P)H:quinone oxidoreductase expression in Cyp1a-knockout and CYP1A-humanized mouse lines and its effect on bioactivation of the carcinogen aristolochic acid I. Toxicol Appl Pharmacol 265(3):360-7. [PubMed: 22982977]  [MGI Ref ID J:192865]

Stiborova M; Levova K; Barta F; Shi Z; Frei E; Schmeiser HH; Nebert DW; Phillips DH; Arlt VM. 2012. Bioactivation versus detoxication of the urothelial carcinogen aristolochic acid I by human cytochrome P450 1A1 and 1A2. Toxicol Sci 125(2):345-58. [PubMed: 22086975]  [MGI Ref ID J:183662]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, mice homozygous for the Cyp1a1/1a2 targeted allele, homozygous for the Ahrd allele, and hemizygous for the hCYP1A1_1A2 transgene may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2450.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3185.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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JAX® Mice
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JAX® Services
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Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
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Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


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