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

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Ahr^tm1Bra targeted mutation are viable and fertile. Homozygotes do not respond to aryl-hydrocarbon receptor agonists. They show reduced liver weight (25% decrease) delayed extramedullary hematopoiesis, and transient hepatic microvesicular steatosis.

Development
The strain was developed using a construct that replaced exon 2 of the endogenous gene with the neomycin gene. The construct was electroporated into both (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells and CCE-derived 129S6/SvEvTac ES cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and transfered into pseudopregnant CD1 foster mothers. Chimeric males were bred to C57BL/6 females. Heterozygous mice were bred to generate homozygotes.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Ahr^tm1Bra allele

002831

B6.129-Ahrtm1Bra/J

View Strains carrying   Ahr^tm1Bra     (1 strain)

Strains carrying other alleles of Ahr

002920	B6(D2N).Spretus-Ahrb-3/J
006203	B6.129(FVB)-Ahrtm3.1Bra/J
002921	B6.D2N-Ahrd/J
002937	D2.B6-Ahrb-1/J

View Strains carrying other alleles of Ahr     (4 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Ahr^tm1Bra/Ahr^tm1Bra

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• growth/size phenotype
• decreased body weight (MGI Ref ID J:33827)
• postnatal growth retardation (MGI Ref ID J:33827)
• hematopoietic system phenotype
• decreased spleen germinal center size (MGI Ref ID J:33827)
  • smaller germinal centers
• enlarged spleen (MGI Ref ID J:33827)
  • exhibited by ~50% at 6 weeks of age
  • increased erythroid component
  • ~50% increase in mononuclear cell numbers at 6 weeks of age, but not at 2 or 3 weeks of age
• extramedullary hematopoiesis (MGI Ref ID J:33827)
  • occuring in postnatal livers
  • varying pentrance, tending to be milder in livers with more severe fatty metamorphosis
• homeostasis/metabolism phenotype
• decreased sensitivity to xenobiotics (MGI Ref ID J:83597)
  • resistance to TCDD-induced toxicity, mutants did not exhibit increased liver weight in response to TCDD administration
• immune system phenotype
• decreased spleen germinal center size (MGI Ref ID J:33827)
  • smaller germinal centers
• enlarged spleen (MGI Ref ID J:33827)
  • exhibited by ~50% at 6 weeks of age
  • increased erythroid component
  • ~50% increase in mononuclear cell numbers at 6 weeks of age, but not at 2 or 3 weeks of age
• liver/biliary system phenotype
• hepatic steatosis (MGI Ref ID J:33827)
  • extensive microvesicular fatty metamorphosis that was neither consistently pericentral or periportal
  • evidence of fatty metamorphosis dissipated by 3 weeks of age
• liver hyperplasia (MGI Ref ID J:33827)
  • hypercellularity with thickening and fibrosis in portal regions by 2 weeks of age
• pale liver (MGI Ref ID J:33827)
  • evident prior to 2 weeks of age
• small liver (MGI Ref ID J:33827)
• decreased liver weight (MGI Ref ID J:83597)
  • reduced liver weight (28% less than wild-type)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Ahr^tm1Bra/Ahr^tm1Bra

        involves: 129S1/Sv * 129X1/SvJ

• cardiovascular system phenotype
• patent ductus venosus (MGI Ref ID J:94465)
  • a patent ductus venosus (shunting blood around the liver) was seen in all mutants
  • exposure to non-teratogenic concentration of dioxin on E18.5 did not result in closure of the ductus venosus in any mutants unlike in Ahr^tm3Bra homozygotes
• endocrine/exocrine gland phenotype
• abnormal ovarian folliculogenesis (MGI Ref ID J:82983)
  • reduced numbers preantral and antral follicles
  • no increase in atresia relative to wild-type
  • increased number of primordial follicles relative to wild-type at 2 to 3 days of age, similar numbers were observed in both mutant and wild-type ovaries between 8 and 53 days of age
  • reduced numbers preantral and antral follicles at 53 days of age
• decreased corpora lutea number (MGI Ref ID J:83527)
  • fewer corpora lutea by 45 days of age
• small ovary (MGI Ref ID J:82983)
• reproductive system phenotype
• abnormal ovarian folliculogenesis (MGI Ref ID J:82983)
  • reduced numbers preantral and antral follicles
  • no increase in atresia relative to wild-type
  • increased number of primordial follicles relative to wild-type at 2 to 3 days of age, similar numbers were observed in both mutant and wild-type ovaries between 8 and 53 days of age
  • reduced numbers preantral and antral follicles at 53 days of age
• abnormal ovulation (MGI Ref ID J:82983)
  • fewer corpora lutea by 45 days of age
• decreased corpora lutea number (MGI Ref ID J:83527)
  • fewer corpora lutea by 45 days of age
• decreased germ cell number (MGI Ref ID J:83527)
  • similar number of germ cells as wild-type at E18
  • 70% reduction in the number of ovarian germ cells at 2 days of age
• small ovary (MGI Ref ID J:82983)

View Research Applications

Research Applications

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

Ahr^tm1Bra related

Cancer Research
Toxicology

Developmental Biology Research
Growth Defects
Internal/Organ Defects (liver)

Hematological Research
Hematopoietic Defects

Internal/Organ Research
Kidney Defects
Liver Defects

Metabolism Research

Research Tools
Toxicology Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ahrtm1Bra
Allele Name		targeted mutation 1, Christopher A Bradfield
Allele Type		Targeted (knock-out)
Common Name(s)		Ahr-; AhrKO;
Mutation Made By		Chris Bradfield,   McArdle Laboratory for Cancer Research
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
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 selection cassette replaced a genomic fragment containing exon 2, which encodes the basic-HLH domain essential for dimerization and DNA binding. Western blot analysis on liver cytosol demonstrated that the protein was not detectable in homozygous mice. [MGI Ref ID J:33827]

Genotyping

Genotyping Information

Genotyping Protocols

Ahr^tm1Bra, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Schmidt JV; Su GH; Reddy JK; Simon MC; Bradfield CA. 1996. Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development. Proc Natl Acad Sci U S A 93(13):6731-6. [PubMed: 8692887]  [MGI Ref ID J:33827]

Additional References

Lahvis GP; Bradfield CA. 1998. Ahr null alleles: distinctive or different? Biochem Pharmacol 56(7):781-7. [PubMed: 9774139]  [MGI Ref ID J:49883]

Ahr^tm1Bra related

Abdelrahim M; Ariazi E; Kim K; Khan S; Barhoumi R; Burghardt R; Liu S; Hill D; Finnell R; Wlodarczyk B; Jordan VC; Safe S. 2006. 3-Methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor alpha. Cancer Res 66(4):2459-67. [PubMed: 16489053]  [MGI Ref ID J:106646]

Baglole CJ; Maggirwar SB; Gasiewicz TA; Thatcher TH; Phipps RP; Sime PJ. 2008. The aryl hydrocarbon receptor attenuates tobacco smoke-induced cyclooxygenase-2 and prostaglandin production in lung fibroblasts through regulation of the NF-kappaB family member RelB. J Biol Chem 283(43):28944-57. [PubMed: 18697742]  [MGI Ref ID J:142470]

Barnett KR; Tomic D; Gupta RK; Babus JK; Roby KF; Terranova PF; Flaws JA. 2007. The aryl hydrocarbon receptor is required for normal gonadotropin responsiveness in the mouse ovary. Toxicol Appl Pharmacol 223(1):66-72. [PubMed: 17594909]  [MGI Ref ID J:124374]

Barnett KR; Tomic D; Gupta RK; Miller KP; Meachum S; Paulose T; Flaws JA. 2007. The aryl hydrocarbon receptor affects mouse ovarian follicle growth via mechanisms involving estradiol regulation and responsiveness. Biol Reprod 76(6):1062-70. [PubMed: 17329597]  [MGI Ref ID J:122009]

Benedict JC; Lin TM; Loeffler IK; Peterson RE; Flaws JA. 2000. Physiological role of the aryl hydrocarbon receptor in mouse ovary development. Toxicol Sci 56(2):382-8. [PubMed: 10910997]  [MGI Ref ID J:83527]

Benedict JC; Miller KP; Lin TM; Greenfeld C; Babus JK; Peterson RE; Flaws JA. 2003. Aryl hydrocarbon receptor regulates growth, but not atresia, of mouse preantral and antral follicles. Biol Reprod 68(5):1511-7. [PubMed: 12606443]  [MGI Ref ID J:82983]

Bunger MK; Glover E; Moran SM; Walisser JA; Lahvis GP; Hsu EL; Bradfield CA. 2008. Abnormal liver development and resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in mice carrying a mutation in the DNA-binding domain of the aryl hydrocarbon receptor. Toxicol Sci 106(1):83-92. [PubMed: 18660548]  [MGI Ref ID J:141978]

Bunger MK; Moran SM; Glover E; Thomae TL; Lahvis GP; Lin BC; Bradfield CA. 2003. Resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity and abnormal liver development in mice carrying a mutation in the nuclear localization sequence of the aryl hydrocarbon receptor. J Biol Chem 278(20):17767-74. [PubMed: 12621046]  [MGI Ref ID J:83597]

Camacho IA; Singh N; Hegde VL; Nagarkatti M; Nagarkatti PS. 2005. Treatment of mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin leads to aryl hydrocarbon receptor-dependent nuclear translocation of NF-kappaB and expression of Fas ligand in thymic stromal cells and consequent apoptosis in T cells. J Immunol 175(1):90-103. [PubMed: 15972635]  [MGI Ref ID J:100624]

Fritz WA; Lin TM; Cardiff RD; Peterson RE. 2007. The aryl hydrocarbon receptor inhibits prostate carcinogenesis in TRAMP mice. Carcinogenesis 28(2):497-505. [PubMed: 17052998]  [MGI Ref ID J:118152]

Fritz WA; Lin TM; Peterson RE. 2008. The aryl hydrocarbon receptor (AhR) inhibits vanadate-induced vascular endothelial growth factor (VEGF) production in TRAMP prostates. Carcinogenesis 29(5):1077-82. [PubMed: 18359762]  [MGI Ref ID J:138497]

Funatake CJ; Marshall NB; Steppan LB; Mourich DV; Kerkvliet NI. 2005. Cutting edge: activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin generates a population of CD4+ CD25+ cells with characteristics of regulatory T cells. J Immunol 175(7):4184-8. [PubMed: 16177056]  [MGI Ref ID J:118998]

Harstad EB; Guite CA; Thomae TL; Bradfield CA. 2006. Liver deformation in Ahr-null mice: evidence for aberrant hepatic perfusion in early development. Mol Pharmacol 69(5):1534-41. [PubMed: 16443691]  [MGI Ref ID J:135797]

Hollingshead BD; Patel RD; Perdew GH. 2006. Endogenous hepatic expression of the hepatitis B virus X-associated protein 2 is adequate for maximal association with aryl hydrocarbon receptor-90-kDa heat shock protein complexes. Mol Pharmacol 70(6):2096-107. [PubMed: 16988012]  [MGI Ref ID J:135626]

Hushka LJ; Williams JS; Greenlee WF. 1998. Characterization of 2,3,7,8-tetrachlorodibenzofuran-dependent suppression and AH receptor pathway gene expression in the developing mouse mammary gland. Toxicol Appl Pharmacol 152(1):200-10. [PubMed: 9772216]  [MGI Ref ID J:51158]

Jiang W; Welty SE; Couroucli XI; Barrios R; Kondraganti SR; Muthiah K; Yu L; Avery SE; Moorthy B. 2004. Disruption of the Ah receptor gene alters the susceptibility of mice to oxygen-mediated regulation of pulmonary and hepatic cytochromes P4501A expression and exacerbates hyperoxic lung injury. J Pharmacol Exp Ther 310(2):512-9. [PubMed: 15123765]  [MGI Ref ID J:100359]

Jurisicova A; Taniuchi A; Li H; Shang Y; Antenos M; Detmar J; Xu J; Matikainen T; Benito Hernandez A; Nunez G; Casper RF. 2007. Maternal exposure to polycyclic aromatic hydrocarbons diminishes murine ovarian reserve via induction of Harakiri. J Clin Invest 117(12):3971-8. [PubMed: 18037991]  [MGI Ref ID J:130754]

Lahvis GP; Lindell SL; Thomas RS; McCuskey RS; Murphy C; Glover E; Bentz M; Southard J; Bradfield CA. 2000. Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice Proc Natl Acad Sci U S A 97(19):10442-7. [PubMed: 10973493]  [MGI Ref ID J:64483]

Lahvis GP; Pyzalski RW; Glover E; Pitot HC; McElwee MK; Bradfield CA. 2005. The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse. Mol Pharmacol 67(3):714-20. [PubMed: 15590894]  [MGI Ref ID J:110128]

Lawrence BP; Roberts AD; Neumiller JJ; Cundiff JA; Woodland DL. 2006. Aryl hydrocarbon receptor activation impairs the priming but not the recall of influenza virus-specific CD8+ T cells in the lung. J Immunol 177(9):5819-28. [PubMed: 17056506]  [MGI Ref ID J:140537]

Lin TM; Ko K; Moore RW; Simanainen U; Oberley TD; Peterson RE. 2002. Effects of aryl hydrocarbon receptor null mutation and in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on prostate and seminal vesicle development in C57BL/6 mice. Toxicol Sci 68(2):479-87. [PubMed: 12151645]  [MGI Ref ID J:126176]

Robles R; Morita Y; Mann KK; Perez GI; Yang S; Matikainen T; Sherr DH; Tilly JL. 2000. The aryl hydrocarbon receptor, a basic helix-loop-helix transcription factor of the PAS gene family, is required for normal ovarian germ cell dynamics in the mouse. Endocrinology 141(1):450-3. [PubMed: 10614669]  [MGI Ref ID J:59155]

Teske S; Bohn AA; Hogaboam JP; Lawrence BP. 2008. Aryl hydrocarbon receptor targets pathways extrinsic to bone marrow cells to enhance neutrophil recruitment during influenza virus infection. Toxicol Sci 102(1):89-99. [PubMed: 18007012]  [MGI Ref ID J:133909]

Thatcher TH; Maggirwar SB; Baglole CJ; Lakatos HF; Gasiewicz TA; Phipps RP; Sime PJ. 2007. Aryl Hydrocarbon Receptor-Deficient Mice Develop Heightened Inflammatory Responses to Cigarette Smoke and Endotoxin Associated with Rapid Loss of the Nuclear Factor-{kappa}B Component RelB. Am J Pathol 170(3):855-64. [PubMed: 17322371]  [MGI Ref ID J:118646]

Thompson KE; Bourguet SM; Christian PJ; Benedict JC; Sipes IG; Flaws JA; Hoyer PB. 2005. Differences between rats and mice in the involvement of the aryl hydrocarbon receptor in 4-vinylcyclohexene diepoxide-induced ovarian follicle loss. Toxicol Appl Pharmacol 203(2):114-23. [PubMed: 15710172]  [MGI Ref ID J:95935]

Veldhoen M; Hirota K; Westendorf AM; Buer J; Dumoutier L; Renauld JC; Stockinger B. 2008. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453(7191):106-9. [PubMed: 18362914]  [MGI Ref ID J:136053]

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]

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	Homozygous females are poor mothers and have small litters. When maintaining a live colony, this strain can be maintained by heterozygous sibling matings. Expected coat color from breeding:Black
Diet Information	LabDiet® 5K52/5K67

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

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(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.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.