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; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N5F4p   Donating Investigator Chris Bradfield,   McArdle Laboratory for Cancer Research

Description
These mice possess loxP sites on either side of exon 2 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Hepatic protein expression of the conditional allele (before exon 2 excision) is equivalent to wildtype by Western blot analysis. This strain may be useful in generating tissue-specific mutants of the floxed allele for use in studies including teratogenesis and xenobiotic metabolism (including dioxin and PCB), Per-Arnt-Sim transcription factors, and fetal vascular development such as ductus venosus closure.

When bred to a strain expressing Cre recombinase in hepatocytes (see Stock No. 003574 for example), this mutant mouse strain may be useful in studies of toxicology.

When bred to a strain expressing Cre recombinase in endothelial cells (see Stock No. 004128 for example), this mutant mouse strain may be useful in studies of vascular development.

Development
A targeting vector was designed to place a loxP-flanked PGK-neo cassette immediately upstream of exon 2 of the endogenous gene, as well as insert a third loxP site downstream of exon 2. The construct was electroporated into 129SvJ-derived GS1 embryonic stem (ES) cells (Genome Systems, St. Louis). Correctly targeted ES cells were injected into C57BL/6J blastocysts. Mice carrying the mutant allele (Ahr^fxneo) were then bred to FVB/N mice with the EIIa-Cre transgene to remove the upstream PGK-neo cassette. After confirmation of PGK-neo excision, mice carrying loxP-flanked exon 2 were then bred to C57BL/6J-background mice for five generations to remove the EIIa-Cre transgene and produce the parental line (Ahr^fx). Because the conditional Ahr^fx allele was generated originally from 129SvJ ES cells that carry the lower affinity Ahr^d allele, the donating investigator used a C57BL/6J strain congenic for DBA2-derived Ahr^d allele to perform all backcrosses (see Stock No. 002921) prior to generating mice homozygous for the Ahr^fx mutation.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ahr

000645	A/HeJ
000646	A/J
000648	AKR/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
002921	B6.D2N-Ahrd/J
002727	B6;129-Ahrtm1Bra/J
001026	BALB/cByJ
000659	C3H/HeJ
000664	C57BL/6J
000669	C58/J
000926	CAROLI/EiJ
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
000671	DBA/2J
000677	MA/MyJ
000550	MOLF/EiJ
001146	SPRET/EiJ

View Strains carrying other alleles of Ahr     (27 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Ahr^tm3.1Bra/Ahr^tm3.1Bra Tg(Alb-cre)21Mgn/0

        B6.Cg-Ahr^tm3.1Bra Tg(Alb-cre)21Mgn   (conditional)

• cardiovascular system phenotype
• *normal* cardiovascular system phenotype (MGI Ref ID J:104388)
  • no defect in the closure of the ductus venosus is seen unlike in mice homozygous for Ahr^tm3Bra
• homeostasis/metabolism phenotype
• decreased physiological sensitivity to xenobiotics (MGI Ref ID J:104388)
  • exposure to 100 ug 2,3,7,8-tetrachlorodibenzo-p-dioxin failed to induce hepatomegaly, or Cyp1a2 expression, only weakly induced Cyp1a1 expression, partially induced Cyp1b1 expression, and resulted in significantly less liver damage compared to homozygous mice lacking the cre transgene
  • however, exposure to 100 ug 2,3,7,8-tetrachlorodibenzo-p-dioxin did induce thymic involution similar to homozygous mice lacking the cre transgene

Ahr^tm3.1Bra/Ahr^tm3.1Bra Tg(Tek-cre)12Flv/0

        B6.Cg-Ahr^tm3.1Bra Tg(Tek-cre)12Flv   (conditional)

• cardiovascular system phenotype
• patent ductus venosus (MGI Ref ID J:104388)
  • 18 of 22 mutants retain a patent ductus venosus as adults

View Research Applications

Research Applications

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

Cancer Research
Toxicology

Cardiovascular Research
Vascular Defects

Cell Biology Research
Transcriptional Regulation

Developmental Biology Research
Internal/Organ Defects
      vasculature

Research Tools
Cancer Research
      genes regulating teratoma development
Cardiovascular Research
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Genetics Research
      Mutagenesis and Transgenesis: transcriptional activation
Toxicology Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ahrtm3.1Bra
Allele Name		targeted mutation 3.1, Christopher A Bradfield
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Ahrfx;
Mutation Made By		Chris Bradfield,   McArdle Laboratory for Cancer Research
Strain of Origin		129/Sv
ES Cell Line Name		GS1
ES Cell Line Strain		129/Sv
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;
Molecular Note		A neomycin resistance cassette was removed via cre-mediated recombination, leaving exon 2 floxed. Western blot of mutant livers confirmed protein was expressed as in wild-type animals. [MGI Ref ID J:104388]

Genotyping

Genotyping Information

Genotyping Protocols

Ahr^tm3.1Bra, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Walisser JA; Glover E; Pande K; Liss AL; Bradfield CA. 2005. Aryl hydrocarbon receptor-dependent liver development and hepatotoxicity are mediated by different cell types. Proc Natl Acad Sci U S A 102(49):17858-63. [PubMed: 16301529]  [MGI Ref ID J:104388]

Additional References

Ahr^tm3.1Bra related

Patel RD; Murray IA; Flaveny CA; Kusnadi A; Perdew GH. 2009. Ah receptor represses acute-phase response gene expression without binding to its cognate response element. Lab Invest 89(6):695-707. [PubMed: 19333233]  [MGI Ref ID J:148793]

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

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are maintained by breeding homozygotes.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. 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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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). This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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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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Contact information

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fax:	207-288-6655

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"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.

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