Overview

Also Known As:Ahr null

These Ahr knock-out mice exhibit hepatic defects.

Donating Investigator

Christopher A Bradfield, University of Wisconsin-Madison

Genetic overview

Genetic Background	Generation

Ahr^tm1Bra

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ahr	aryl-hydrocarbon receptor

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Research Applications

Developmental Biology Research
Hematological Research
Internal/Organ Research
Research Tools
Metabolism Research
Cancer Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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 Suggestions

Wild-type from the colony

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

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):6731-6PubMed: 8692887 MGI: J:33827

View All References

Genetics

Ahr^tm1Bra

Allele Symbol: Ahr^tm1Bra

Allele Name	targeted mutation 1, Christopher A Bradfield
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Ahr^-; AhrKO
Gene Symbol and Name	Ahr, aryl-hydrocarbon receptor
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	12
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.
Mutations Made By	Christopher Bradfield, University of Wisconsin-Madison

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Ahr^tm1Bra related

Developmental Biology Research
- Growth Defects
- Internal/Organ Defects
  - liver
Hematological Research
- Hematopoietic Defects
Internal/Organ Research
- Kidney Defects
- Liver Defects
Research Tools
- Toxicology Research
Metabolism Research
Cancer Research
- Toxicology

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Ahr^tm1Bra/Ahr^tm1Bra
B6.129-Ahr

cardiovascular system phenotype

abnormal blood vessel morphology
- in the eye the limbal vasculature is exaggerated with loops that extend centrally and invade the corneal stroma

abnormal kidney blood vessel morphology
- vascular architecture is altered and appears less dense

abnormal liver sinusoid morphology
- the sinusoidal pattern retains the neonatal structure with failure of the resolution of sinusoidal junctions that normally occurs during liver development
- sinusoids are highly anastomotic throughout the liver

patent ductus venosus
- the ductus venosus remains open in adults resulting in portosystemic shunting and impaired liver perfusion

growth/size/body region phenotype

increased body weight
- 7% heavier than littermate controls of P90

homeostasis/metabolism phenotype

decreased physiological sensitivity to xenobiotic
- exposure to 2,3,7,8-tetrachrlorodibenzo-p-dioxin (TCDD) has no effect on anterior, ventral or dorsolateral prostate weights unlike in similarly exposed littermate controls
- exposure to TCDD increased rather than decreased seminal vesicle weight on P35
- Normal - however, by P90 seminal vesicle weight is reduced

abnormal circulating hormone level
- serum concentration of 5alpha-androstane-3alpha,17beta-diol are reduced at P21

liver/biliary system phenotype

decreased liver weight
- about a 25% reduction in relative liver weight compared to controls

abnormal liver sinusoid morphology
- the sinusoidal pattern retains the neonatal structure with failure of the resolution of sinusoidal junctions that normally occurs during liver development
- sinusoids are highly anastomotic throughout the liver

abnormal hepatocyte morphology
- cytoplasmic area is reduced by nearly 50% compared to control littermates
- total cellular area is reduced by about 36% compared to control littermates

renal/urinary system phenotype

abnormal kidney blood vessel morphology
- vascular architecture is altered and appears less dense

reproductive system phenotype

small prostate gland anterior lobe
- anterior prostate weight is reduced on P35 but not on P90

small prostate gland dorsolateral lobe
- dorsolateral prostate weight is reduced on P35 and P90

decreased seminal vesicle weight
- on P35 and P90

vision/eye phenotype

persistent hyaloid artery
- in 25% of mice the hyaloid artery extends to the posterior lens capsule membrane
- a persistent hyaloid artery is commonly seen

cellular phenotype

patent ductus venosus
- the ductus venosus remains open in adults resulting in portosystemic shunting and impaired liver perfusion

endocrine/exocrine gland phenotype

small prostate gland anterior lobe
- anterior prostate weight is reduced on P35 but not on P90

decreased seminal vesicle weight
- on P35 and P90

small prostate gland dorsolateral lobe
- dorsolateral prostate weight is reduced on P35 and P90

Genotype: Ahr^tm1Bra/Ahr^tm1Bra
involves: 129S1/Sv * 129X1/SvJ

integument phenotype

abnormal branching of the mammary ductal tree
- the number of terminal end buds is reduced by about 50% compared to littermate controls most ducts appear to be blunt ended or narrowed at the tip

cardiovascular system phenotype

patent ductus venosus
- 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
- in all mice
- a patent ductus venosus (shunting blood around the liver) was seen in all mutants

reproductive system phenotype

abnormal ovulation
- fewer corpora lutea by 45 days of age

abnormal superovulation
- following treatment with low doses of exogenous gonadotropins fewer oocytes are collected compared to similarly treated controls
- Normal - however, ovulation in response to higher doses of exogenous gonadotropins is similar to controls

decreased ovary weight
- following treatment with a low dose equine chorionic gonadotropin (eCG) ovarian weights are significantly less than similarly treated controls
- Normal - however, in the absence of treatment or after treatment with a high dose of eCG ovarian weights are similar to controls

abnormal ovarian folliculogenesis
- 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
- reduced numbers preantral and antral follicles at 53 days of age

decreased corpora lutea number
- fewer corpora lutea by 45 days of age

decreased germ cell number
- 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

abnormal ovary physiology
- following treatment with a low dose equine chorionic gonadotropin (eCG) fewer corpora lutea are present compared to similarly treated controls

cellular phenotype

patent ductus venosus
- 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
- in all mice

decreased germ cell number
- 70% reduction in the number of ovarian germ cells at 2 days of age
- similar number of germ cells as wild-type at E18

endocrine/exocrine gland phenotype

abnormal branching of the mammary ductal tree
- the number of terminal end buds is reduced by about 50% compared to littermate controls most ducts appear to be blunt ended or narrowed at the tip

decreased ovary weight
- Normal - however, in the absence of treatment or after treatment with a high dose of eCG ovarian weights are similar to controls
- following treatment with a low dose equine chorionic gonadotropin (eCG) ovarian weights are significantly less than similarly treated controls

abnormal ovarian folliculogenesis
- 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
- reduced numbers preantral and antral follicles

small ovary

decreased corpora lutea number
- fewer corpora lutea by 45 days of age

abnormal ovary physiology
- following treatment with a low dose equine chorionic gonadotropin (eCG) fewer corpora lutea are present compared to similarly treated controls

Genotype: Ahr^tm1Bra/Ahr^tm1Bra
B6.129-Ahr/J

immune system phenotype

abnormal chemokine level
- basal and 4 h post cigarette smoke exposure levels of CXCL2 and PGE2 are increased in BAL fluid relative to similarly treated controls
- levels of proinflammatory chemokines are increased in bronchoalveolar lavage (BAL) fluid

increased susceptibility to bacterial infection
- inflammatory response in the lungs following aerosol exposure to LPS is increased compared to similarly treated controls
- macrophages from BAL fluid exposed to LPS in vitro produce more IL6 and TNF

abnormal interleukin level
- increased levels of IL6 in BAL fluid

abnormal macrophage physiology
- Normal - exposure to an NFKB inhibitor (helenalin or SN50) blocks LPS induced IL6 and TNF expression in both mutant and wild-type mice
- macrophages from BAL fluid exposed to LPS in vitro produce more IL6 and TNF

lung inflammation
- following cigarette smoke exposure perivascular infiltrates are more pronounced
- inflammatory response in the lungs following aerosol exposure to LPS is increased compared to similarly treated controls
- lung inflammation after exposure to hyperoxia is increased compared to wild-type controls
- following cigarette smoke exposure neutrophil influx into and beta-glucuronidase activity in the lungs are increased compared to similarly exposed wild-type controls

abnormal cytokine level
- levels of proinflammatory cytokines are increased in bronchoalveolar lavage (BAL) fluid

abnormal tumor necrosis factor level
- both basal levels and expression 4 h after cigarette smoke exposure are increased in BAL fluid relative to similarly treated controls

endocrine/exocrine gland phenotype

abnormal primordial ovarian follicle morphology
- at P4 the number of primordial follicles is increased about 2 fold compared to littermate controls

abnormal ovary physiology
- cultured fetal ovaries show a decrease in the number of apoptotic germ cells

hematopoietic system phenotype

abnormal macrophage physiology
- Normal - exposure to an NFKB inhibitor (helenalin or SN50) blocks LPS induced IL6 and TNF expression in both mutant and wild-type mice
- macrophages from BAL fluid exposed to LPS in vitro produce more IL6 and TNF

reproductive system phenotype

abnormal primordial ovarian follicle morphology
- at P4 the number of primordial follicles is increased about 2 fold compared to littermate controls

abnormal ovary physiology
- cultured fetal ovaries show a decrease in the number of apoptotic germ cells

respiratory system phenotype

pulmonary edema
- severe edema is seen after exposure to hyperoxia

lung inflammation
- inflammatory response in the lungs following aerosol exposure to LPS is increased compared to similarly treated controls
- lung inflammation after exposure to hyperoxia is increased compared to wild-type controls
- following cigarette smoke exposure neutrophil influx into and beta-glucuronidase activity in the lungs are increased compared to similarly exposed wild-type controls
- following cigarette smoke exposure perivascular infiltrates are more pronounced

pulmonary alveolar edema
- severe alveolar flooding after exposure to hyperoxia

homeostasis/metabolism phenotype

abnormal cytokine level
- levels of proinflammatory cytokines are increased in bronchoalveolar lavage (BAL) fluid

abnormal tumor necrosis factor level
- both basal levels and expression 4 h after cigarette smoke exposure are increased in BAL fluid relative to similarly treated controls

increased physiological sensitivity to xenobiotic
- following cigarette smoke exposure perivascular infiltrates are more pronounced in the lungs
- following cigarette smoke exposure neutrophil influx into and beta-glucuronidase activity in the lungs are increased compared to similarly exposed wild-type controls

abnormal chemokine level
- basal and 4 h post cigarette smoke exposure levels of CXCL2 and PGE2 are increased in BAL fluid relative to similarly treated controls
- levels of proinflammatory chemokines are increased in bronchoalveolar lavage (BAL) fluid

abnormal interleukin level
- increased levels of IL6 in BAL fluid

pulmonary edema
- severe edema is seen after exposure to hyperoxia

abnormal enzyme/coenzyme activity
- basal hepatic methoxyresorufin O-demethylase (MROD) activity is reduced
- Normal - however, hyperoxia still induces an increase in MROD activity
- basal pulmonary ethoxyresorufin O-deethylase (EROD) activity is reduced and exposure to hyperoxia fails to increase pulmonary or hepatic EROD activity

increased susceptibility to injury
- mice are more susceptible to hyperoxia induced lung injury with severe alveolar flooding, pulmonary edema, and increased lung inflammation

pulmonary alveolar edema
- severe alveolar flooding after exposure to hyperoxia

The following phenotype relates to a compound genotype created using this strain

Genotype: Ahr^tm1Bra/Ahr^tm1Bra
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

cardiovascular system phenotype

patent ductus venosus

hematopoietic system phenotype

extramedullary hematopoiesis
- occuring in postnatal livers
- varying penetrance, tending to be milder in livers with more severe fatty metamorphosis

abnormal Langerhans cell morphology
- immature cells are slightly smaller and remain of lower granularity after maturation compared to controls
- expression analysis indicates impaired maturation after 3 days in culture

enlarged spleen
- increased erythroid component
- exhibited by ~50% at 6 weeks of age
- ~50% increase in mononuclear cell numbers at 6 weeks of age, but not at 2 or 3 weeks of age

decreased spleen germinal center size
- smaller germinal centers

homeostasis/metabolism phenotype

decreased physiological sensitivity to xenobiotic
- resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced toxicity; mutants do not exhibit hepatomegaly, thymic involution or cleft palate formation in response to TCDD administration

cellular phenotype

patent ductus venosus

immune system phenotype

abnormal Langerhans cell physiology
- expression of CD24a is reduced on immature and mature Langerhans cells
- after 45, but not after 90, minutes in culture phagocytic activity is increased

abnormal cytokine secretion
- secretion of granulocyte macrophage colony stimulating factor (CSF2) is reduced in cultured epidermal cells (about 90% keratinocytes)

enlarged spleen
- 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

abnormal Langerhans cell morphology
- immature cells are slightly smaller and remain of lower granularity after maturation compared to controls
- expression analysis indicates impaired maturation after 3 days in culture

decreased susceptibility to type IV hypersensitivity reaction
- the increase in ear thickness following exposure to fluorescein isothiocyanate (FITC) is decreased compared to similarly treated controls

decreased spleen germinal center size
- smaller germinal centers

integument phenotype

abnormal keratinocyte physiology
- secretion of granulocyte macrophage colony stimulating factor (CSF2) is reduced in cultured epidermal cells (about 90% keratinocytes)

endocrine/exocrine gland phenotype

abnormal primordial ovarian follicle morphology
- at P4 the number of primordial follicles is increased about 2 fold compared to littermate controls

liver/biliary system phenotype

microvesicular hepatic steatosis
- evidence of fatty metamorphosis dissipated by 3 weeks of age
- extensive microvesicular fatty metamorphosis that was neither consistently pericentral or periportal

hepatic steatosis
- evidence of fatty metamorphosis dissipated by 3 weeks of age
- extensive microvesicular fatty metamorphosis that was neither consistently pericentral or periportal

pale liver
- evident prior to 2 weeks of age

small liver

liver hyperplasia
- hypercellularity with thickening and fibrosis in portal regions by 2 weeks of age

decreased liver weight
- reduced liver weight (28% less than wild-type)

reproductive system phenotype

abnormal primordial ovarian follicle morphology
- at P4 the number of primordial follicles is increased about 2 fold compared to littermate controls

growth/size/body region phenotype

enlarged spleen
- ~50% increase in mononuclear cell numbers at 6 weeks of age, but not at 2 or 3 weeks of age
- increased erythroid component
- exhibited by ~50% at 6 weeks of age

decreased body weight

liver hyperplasia
- hypercellularity with thickening and fibrosis in portal regions by 2 weeks of age

postnatal growth retardation

References

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):6731-6PubMed: 8692887 MGI: J:33827

Additional References

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

Additional - Ahr^tm1Bra related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Ahr
- Standard PCR:Ahr Alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

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
- Additional Breeding and Husbandry Support
Appearance
- black
  Related Genotype: a/a
Citation
When using the Ahr null mouse strain in a publication, please cite the originating article(s) and include JAX stock #002727 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Ahr<tm1Bra>

Related Products and Services

Frozen Mouse Embryo	B6;129-Ahr<tm1Bra>/J	$2595.00
Frozen Mouse Embryo	B6;129-Ahr<tm1Bra>/J	$2595.00
Frozen Mouse Embryo	B6;129-Ahr<tm1Bra>/J	$3373.50
Frozen Mouse Embryo	B6;129-Ahr<tm1Bra>/J	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Ahr null

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Ahrtm1Bra

Allele Symbol: Ahrtm1Bra

Disease Terms

Research Areas By Phenotype

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

Genotype: Ahrtm1Bra related

Mammalian Phenotype Terms by Genotype

Genotype: Ahrtm1Bra/Ahrtm1BraB6.129-Ahr

cardiovascular system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

liver/biliary system phenotype

renal/urinary system phenotype

reproductive system phenotype

vision/eye phenotype

cellular phenotype

endocrine/exocrine gland phenotype

Genotype: Ahrtm1Bra/Ahrtm1Brainvolves: 129S1/Sv * 129X1/SvJ

integument phenotype

cardiovascular system phenotype

reproductive system phenotype

cellular phenotype

endocrine/exocrine gland phenotype

Genotype: Ahrtm1Bra/Ahrtm1BraB6.129-Ahr/J

immune system phenotype

endocrine/exocrine gland phenotype

hematopoietic system phenotype

reproductive system phenotype

respiratory system phenotype

homeostasis/metabolism phenotype

Genotype: Ahrtm1Bra/Ahrtm1Brainvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

cardiovascular system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

cellular phenotype

immune system phenotype

integument phenotype

endocrine/exocrine gland phenotype

liver/biliary system phenotype

reproductive system phenotype

growth/size/body region phenotype

References

Additional References

Additional - Ahrtm1Bra related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Ahr^tm1Bra

Allele Symbol: Ahr^tm1Bra

Genotype: Ahr^tm1Bra related

Genotype: Ahr^tm1Bra/Ahr^tm1Bra
B6.129-Ahr

Genotype: Ahr^tm1Bra/Ahr^tm1Bra
involves: 129S1/Sv * 129X1/SvJ

Genotype: Ahr^tm1Bra/Ahr^tm1Bra
B6.129-Ahr/J

Genotype: Ahr^tm1Bra/Ahr^tm1Bra
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Ahr^tm1Bra related