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 N5F3pF2p Generation Definitions   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

000690	129P3/J
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
008599	B6.Cg-Cyp1a2/Cyp1a1tm2Dwn Ahrd Tg(CYP1A1,CYP1A2)1Dwn/DwnJ
002921	B6.D2N-Ahrd/J
002727	B6;129-Ahrtm1Bra/J
001026	BALB/cByJ
000652	BDP/J
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
000928	CAST/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
000671	DBA/2J
000673	HRS/J
000674	I/LnJ
000675	LG/J
000676	LP/J
000677	MA/MyJ
000550	MOLF/EiJ
000684	NZB/BlNJ
000679	P/J
000930	PERA/EiJ
000726	RBF/DnJ
000682	RF/J
000644	SEA/GnJ
000280	SF/CamEiJ
000686	SJL/J
001146	SPRET/EiJ
000688	ST/bJ
000689	SWR/J
000693	WC/ReJ KitlSl/J
000933	YBR/EiJ

View Strains carrying other alleles of Ahr     (55 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      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
  • no defect in the closure of the ductus venosus is seen unlike in mice homozygous for Ahr^tm3Bra   (MGI Ref ID J:104388)
• homeostasis/metabolism phenotype
• decreased physiological sensitivity to xenobiotic
  • 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   (MGI Ref ID J:104388)
  • however, exposure to 100 ug 2,3,7,8-tetrachlorodibenzo-p-dioxin did induce thymic involution similar to homozygous mice lacking the cre transgene   (MGI Ref ID J:104388)

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

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
      Mutagenesis and Transgenesis: transcriptional activation
Toxicology Research

Genes & Alleles

Gene & Allele Information provided by MGI

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 provided by MGI

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

Agbor LN; Elased KM; Walker MK. 2011. Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness. Biochem Pharmacol 82(5):514-23. [PubMed: 21684261]  [MGI Ref ID J:175457]

Jux B; Kadow S; Luecke S; Rannug A; Krutmann J; Esser C. 2011. The aryl hydrocarbon receptor mediates UVB radiation-induced skin tanning. J Invest Dermatol 131(1):203-10. [PubMed: 20861855]  [MGI Ref ID J:179854]

Kadow S; Jux B; Zahner SP; Wingerath B; Chmill S; Clausen BE; Hengstler J; Esser C. 2011. Aryl hydrocarbon receptor is critical for homeostasis of invariant gammadelta T cells in the murine epidermis. J Immunol 187(6):3104-10. [PubMed: 21844385]  [MGI Ref ID J:179245]

Kiss EA; Vonarbourg C; Kopfmann S; Hobeika E; Finke D; Esser C; Diefenbach A. 2011. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science 334(6062):1561-5. [PubMed: 22033518]  [MGI Ref ID J:179017]

Li Y; Innocentin S; Withers DR; Roberts NA; Gallagher AR; Grigorieva EF; Wilhelm C; Veldhoen M. 2011. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147(3):629-40. [PubMed: 21999944]  [MGI Ref ID J:178527]

Nakahama T; Kimura A; Nguyen NT; Chinen I; Hanieh H; Nohara K; Fujii-Kuriyama Y; Kishimoto T. 2011. Aryl hydrocarbon receptor deficiency in T cells suppresses the development of collagen-induced arthritis. Proc Natl Acad Sci U S A 108(34):14222-7. [PubMed: 21825138]  [MGI Ref ID J:175988]

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]

Sekine H; Mimura J; Oshima M; Okawa H; Kanno J; Igarashi K; Gonzalez FJ; Ikuta T; Kawajiri K; Fujii-Kuriyama Y. 2009. Hypersensitivity of aryl hydrocarbon receptor-deficient mice to lipopolysaccharide-induced septic shock. Mol Cell Biol 29(24):6391-400. [PubMed: 19822660]  [MGI Ref ID J:155121]

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, RG10/RG30.

Colony Maintenance

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

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J	(approximate)
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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

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.

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.