Phenotypes associated with this allele

• Allele Symbol: Ahr^tm1Bra
• Allele Name: targeted mutation 1, Christopher A Bradfield
• Allele ID: MGI:1857427
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ahr^tm1Bra/Ahr^tm1Bra	B6.129-Ahr^tm1Bra	MGI:4361635
hm2	Ahr^tm1Bra/Ahr^tm1Bra	B6.129-Ahr^tm1Bra/J	MGI:4361634
hm3	Ahr^tm1Bra/Ahr^tm1Bra	involves: 129S1/Sv * 129X1/SvJ	MGI:2661863
hm4	Ahr^tm1Bra/Ahr^tm1Bra	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:2661849
cx5	Ahr^tm1Bra/Ahr^tm1Bra Tg(TRAMP)8247Ng/0	B6.Cg-Ahr^tm1Bra Tg(TRAMP)8247Ng	MGI:4361636
cx6	Ahr^tm1Bra/Ahr^+ Tg(TRAMP)8247Ng/0	B6.Cg-Ahr^tm1Bra Tg(TRAMP)8247Ng	MGI:4361637

Genotype
MGI:4361635

hm1

• Allelic Composition: Ahr^tm1Bra/Ahr^tm1Bra
• Genetic Background: B6.129-Ahr^tm1Bra

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

abnormal circulating hormone level ( J:126176 )

• serum concentration of 5alpha-androstane-3alpha,17beta-diol are reduced at P21

decreased physiological sensitivity to xenobiotic ( J:126176 )

• 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

• however, by P90 seminal vesicle weight is reduced

cardiovascular system

abnormal eye vasculature morphology ( J:64483 )

• in the eye the limbal vasculature is exaggerated with loops that extend centrally and invade the corneal stroma

persistent hyaloid artery ( J:64483 )

• a persistent hyaloid artery is commonly seen

• in 25% of mice the hyaloid artery extends to the posterior lens capsule membrane

abnormal kidney vasculature morphology ( J:64483 )

• vascular architecture is altered and appears less dense

abnormal liver sinusoid morphology ( J:64483 )

• 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 ( J:64483 )

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

liver/biliary system

abnormal liver sinusoid morphology ( J:64483 )

• 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 ( J:64483 )

• total cellular area is reduced by about 36% compared to control littermates

• cytoplasmic area is reduced by nearly 50% compared to control littermates

decreased liver weight ( J:64483 )

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

vision/eye

abnormal eye vasculature morphology ( J:64483 )

• in the eye the limbal vasculature is exaggerated with loops that extend centrally and invade the corneal stroma

persistent hyaloid artery ( J:64483 )

• a persistent hyaloid artery is commonly seen

• in 25% of mice the hyaloid artery extends to the posterior lens capsule membrane

reproductive system

decreased prostate gland anterior lobe weight ( J:126176 )

♂ • anterior prostate weight is reduced on P35 but not on P90

decreased prostate gland dorsolateral lobe weight ( J:126176 )

♂ • dorsolateral prostate weight is reduced on P35 and P90

decreased seminal vesicle weight ( J:126176 )

♂ • on P35 and P90

growth/size/body

increased body weight ( J:126176 )

• 7% heavier than littermate controls of P90

endocrine/exocrine glands

decreased prostate gland anterior lobe weight ( J:126176 )

♂ • anterior prostate weight is reduced on P35 but not on P90

decreased prostate gland dorsolateral lobe weight ( J:126176 )

♂ • dorsolateral prostate weight is reduced on P35 and P90

decreased seminal vesicle weight ( J:126176 )

♂ • on P35 and P90

renal/urinary system

abnormal kidney vasculature morphology ( J:64483 )

• vascular architecture is altered and appears less dense

cellular

patent ductus venosus ( J:64483 )

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

Genotype
MGI:4361634

hm2

• Allelic Composition: Ahr^tm1Bra/Ahr^tm1Bra
• Genetic Background: B6.129-Ahr^tm1Bra/J

homeostasis/metabolism

pulmonary edema ( J:100359 )

• severe edema is seen after exposure to hyperoxia

pulmonary alveolar edema ( J:100359 )

• severe alveolar flooding after exposure to hyperoxia

abnormal cytokine level ( J:118646 )

• levels of proinflammatory cytokines are increased in bronchoalveolar lavage (BAL) fluid

abnormal chemokine level ( J:118646 )

• levels of proinflammatory chemokines are increased in bronchoalveolar lavage (BAL) fluid

• basal and 4 h post cigarette smoke exposure levels of CXCL2 and PGE2 are increased in BAL fluid relative to similarly treated controls

abnormal interleukin level ( J:118646 )

• increased levels of IL6 in BAL fluid

abnormal tumor necrosis factor level ( J:118646 )

• both basal levels and expression 4 h after cigarette smoke exposure are increased in BAL fluid relative to similarly treated controls

abnormal enzyme/coenzyme activity ( J:100359 )

• basal pulmonary ethoxyresorufin O-deethylase (EROD) activity is reduced and exposure to hyperoxia fails to increase pulmonary or hepatic EROD activity

• basal hepatic methoxyresorufin O-demethylase (MROD) activity is reduced

• however, hyperoxia still induces an increase in MROD activity

increased physiological sensitivity to xenobiotic ( J:118646 )

• 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 in the lungs

increased susceptibility to injury ( J:100359 )

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

reproductive system

increased primordial ovarian follicle number ( J:59155 )

♀ • at P4 the number of primordial follicles is increased about 2 fold compared to littermate controls

abnormal ovary physiology ( J:59155 )

♀ • cultured fetal ovaries show a decrease in the number of apoptotic germ cells

immune system

abnormal macrophage physiology ( J:118646 )

• macrophages from BAL fluid exposed to LPS in vitro produce more IL6 and TNF

• exposure to an NFKB inhibitor (helenalin or SN50) blocks LPS induced IL6 and TNF expression in both mutant and wild-type mice

abnormal cytokine level ( J:118646 )

• levels of proinflammatory cytokines are increased in bronchoalveolar lavage (BAL) fluid

abnormal chemokine level ( J:118646 )

• levels of proinflammatory chemokines are increased in bronchoalveolar lavage (BAL) fluid

• basal and 4 h post cigarette smoke exposure levels of CXCL2 and PGE2 are increased in BAL fluid relative to similarly treated controls

abnormal interleukin level ( J:118646 )

• increased levels of IL6 in BAL fluid

abnormal tumor necrosis factor level ( J:118646 )

• both basal levels and expression 4 h after cigarette smoke exposure are increased in BAL fluid relative to similarly treated controls

lung inflammation ( J:100359 , J:118646 )

• lung inflammation after exposure to hyperoxia is increased compared to wild-type controls (J:100359)

• following cigarette smoke exposure neutrophil influx into and beta-glucuronidase activity in the lungs are increased compared to similarly exposed wild-type controls (J:118646)

• following cigarette smoke exposure perivascular infiltrates are more pronounced (J:118646)

• inflammatory response in the lungs following aerosol exposure to LPS is increased compared to similarly treated controls (J:118646)

increased susceptibility to bacterial infection ( J:118646 )

• 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

endocrine/exocrine glands

increased primordial ovarian follicle number ( J:59155 )

♀ • at P4 the number of primordial follicles is increased about 2 fold compared to littermate controls

abnormal ovary physiology ( J:59155 )

♀ • cultured fetal ovaries show a decrease in the number of apoptotic germ cells

respiratory system

pulmonary edema ( J:100359 )

• severe edema is seen after exposure to hyperoxia

pulmonary alveolar edema ( J:100359 )

• severe alveolar flooding after exposure to hyperoxia

lung inflammation ( J:100359 , J:118646 )

• lung inflammation after exposure to hyperoxia is increased compared to wild-type controls (J:100359)

• following cigarette smoke exposure neutrophil influx into and beta-glucuronidase activity in the lungs are increased compared to similarly exposed wild-type controls (J:118646)

• following cigarette smoke exposure perivascular infiltrates are more pronounced (J:118646)

• inflammatory response in the lungs following aerosol exposure to LPS is increased compared to similarly treated controls (J:118646)

hematopoietic system

abnormal macrophage physiology ( J:118646 )

• macrophages from BAL fluid exposed to LPS in vitro produce more IL6 and TNF

• exposure to an NFKB inhibitor (helenalin or SN50) blocks LPS induced IL6 and TNF expression in both mutant and wild-type mice

Genotype
MGI:2661863

hm3

• Allelic Composition: Ahr^tm1Bra/Ahr^tm1Bra
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

cardiovascular system

patent ductus venosus ( J:94465 , J:166864 )

• a patent ductus venosus (shunting blood around the liver) was seen in all mutants (J:94465)

• 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 (J:94465)

• in all mice (J:166864)

reproductive system

decreased germ cell number ( 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

decreased corpora lutea number ( J:83527 )

♀ • fewer corpora lutea by 45 days of age

increased primordial ovarian follicle number ( J:83527 )

♀ • 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

decreased secondary ovarian follicle number ( J:82983 , J:83527 )

♀ • reduced numbers of preantral follicles (J:82983)

♀ • reduced numbers of preantral follicles at 53 days of age (J:83527)

decreased tertiary ovarian follicle number ( J:82983 , J:83527 )

♀ • reduced numbers of antral follicles (J:82983)

♀ • reduced numbers of antral follicles at 53 days of age (J:83527)

abnormal ovarian folliculogenesis ( J:82983 )

♀ • reduced follicular growth

♀ • no increase in atresia relative to wild-type

small ovary ( J:82983 )

♀

decreased ovary weight ( J:124374 )

♀ • following treatment with a low dose equine chorionic gonadotropin (eCG) ovarian weights are significantly less than similarly treated controls

♀ • however, in the absence of treatment or after treatment with a high dose of eCG ovarian weights are similar to controls

abnormal ovary physiology ( J:124374 )

♀ • following treatment with a low dose equine chorionic gonadotropin (eCG) fewer corpora lutea are present compared to similarly treated controls

abnormal ovulation ( J:82983 )

♀ • fewer corpora lutea by 45 days of age

decreased superovulation rate ( J:124374 )

♀ • following treatment with low doses of exogenous gonadotropins fewer oocytes are collected compared to similarly treated controls

♀ • however, ovulation in response to higher doses of exogenous gonadotropins is similar to controls

endocrine/exocrine glands

abnormal branching of the mammary ductal tree ( J:51158 )

♀ • 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 corpora lutea number ( J:83527 )

♀ • fewer corpora lutea by 45 days of age

increased primordial ovarian follicle number ( J:83527 )

♀ • 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

decreased secondary ovarian follicle number ( J:82983 , J:83527 )

♀ • reduced numbers of preantral follicles (J:82983)

♀ • reduced numbers of preantral follicles at 53 days of age (J:83527)

decreased tertiary ovarian follicle number ( J:82983 , J:83527 )

♀ • reduced numbers of antral follicles (J:82983)

♀ • reduced numbers of antral follicles at 53 days of age (J:83527)

abnormal ovarian folliculogenesis ( J:82983 )

♀ • reduced follicular growth

♀ • no increase in atresia relative to wild-type

small ovary ( J:82983 )

♀

decreased ovary weight ( J:124374 )

♀ • following treatment with a low dose equine chorionic gonadotropin (eCG) ovarian weights are significantly less than similarly treated controls

♀ • however, in the absence of treatment or after treatment with a high dose of eCG ovarian weights are similar to controls

abnormal ovary physiology ( J:124374 )

♀ • following treatment with a low dose equine chorionic gonadotropin (eCG) fewer corpora lutea are present compared to similarly treated controls

integument

abnormal branching of the mammary ductal tree ( J:51158 )

♀ • 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

cellular

patent ductus venosus ( J:94465 , J:166864 )

• a patent ductus venosus (shunting blood around the liver) was seen in all mutants (J:94465)

• 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 (J:94465)

• in all mice (J:166864)

decreased germ cell number ( 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

Genotype
MGI:2661849

hm4

• Allelic Composition: Ahr^tm1Bra/Ahr^tm1Bra
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Liver abnormalities in Ahr^tm1Bra/Ahr^tm1Bra mice

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:83597 )

• 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

cardiovascular system

patent ductus venosus ( J:83597 )

growth/size/body

decreased body weight ( J:33827 )

postnatal growth retardation ( J:33827 )

liver hyperplasia ( J:33827 )

• hypercellularity with thickening and fibrosis in portal regions by 2 weeks of age

enlarged spleen ( 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

immune system

enlarged spleen ( 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

abnormal Langerhans cell morphology ( J:148870 )

• expression analysis indicates impaired maturation after 3 days in culture

• immature cells are slightly smaller and remain of lower granularity after maturation compared to controls

decreased spleen germinal center size ( J:33827 )

• smaller germinal centers

abnormal Langerhans cell physiology ( J:148870 )

• expression of CD24a is reduced on immature and mature Langerhans cells

• after 45, but not after 90, minutes in culture phagocytic activity is increased

decreased susceptibility to type IV hypersensitivity reaction ( J:148870 )

• the increase in ear thickness following exposure to fluorescein isothiocyanate (FITC) is decreased compared to similarly treated controls

abnormal cytokine secretion ( J:148870 )

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

liver/biliary system

liver hyperplasia ( J:33827 )

• hypercellularity with thickening and fibrosis in portal regions by 2 weeks of age

small liver ( J:33827 )

decreased liver weight ( J:83597 )

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

microvesicular hepatic steatosis ( J:33827 )

• extensive microvesicular fatty metamorphosis that was neither consistently pericentral or periportal

• evidence of fatty metamorphosis dissipated by 3 weeks of age

pale liver ( J:33827 )

• evident prior to 2 weeks of age

reproductive system

increased primordial ovarian follicle number ( J:59155 )

♀ • at P4 the number of primordial follicles is increased about 2 fold compared to littermate controls

endocrine/exocrine glands

increased primordial ovarian follicle number ( J:59155 )

♀ • at P4 the number of primordial follicles is increased about 2 fold compared to littermate controls

hematopoietic system

enlarged spleen ( 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 ( J:33827 )

• occuring in postnatal livers

• varying penetrance, tending to be milder in livers with more severe fatty metamorphosis

abnormal Langerhans cell morphology ( J:148870 )

• expression analysis indicates impaired maturation after 3 days in culture

• immature cells are slightly smaller and remain of lower granularity after maturation compared to controls

decreased spleen germinal center size ( J:33827 )

• smaller germinal centers

integument

abnormal keratinocyte physiology ( J:148870 )

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

cellular

patent ductus venosus ( J:83597 )

Genotype
MGI:4361636

cx5

• Allelic Composition: Ahr^tm1Bra/Ahr^tm1Bra; Tg(TRAMP)8247Ng/0
• Genetic Background: B6.Cg-Ahr^tm1Bra Tg(TRAMP)8247Ng

neoplasm

increased prostate gland tumor incidence ( J:118152 )

♂ • at 140 days of age the incidence of prostate tumors is increased compared to transgenic mice wild-type for Ahr

♂ • at 210 days of age the total number of lymph node metastases is increased but when normalized for the increased number parent tumors no significant difference is seen

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:118152 )

♂ • at 140 days of age the incidence of prostate tumors is increased compared to transgenic mice wild-type for Ahr

♂ • at 210 days of age the total number of lymph node metastases is increased but when normalized for the increased number parent tumors no significant difference is seen

reproductive system

increased prostate gland tumor incidence ( J:118152 )

♂ • at 140 days of age the incidence of prostate tumors is increased compared to transgenic mice wild-type for Ahr

♂ • at 210 days of age the total number of lymph node metastases is increased but when normalized for the increased number parent tumors no significant difference is seen

Genotype
MGI:4361637

cx6

• Allelic Composition: Ahr^tm1Bra/Ahr⁺; Tg(TRAMP)8247Ng/0
• Genetic Background: B6.Cg-Ahr^tm1Bra Tg(TRAMP)8247Ng

neoplasm

increased prostate gland tumor incidence ( J:118152 )

♂ • at 140 days of age the incidence of prostate tumors is increased compared to transgenic mice wild-type for Ahr

♂ • at 175 days of age the total number of lymph node metastases is increased but when normalized for the increased number parent tumors no significant difference is seen

reproductive system

increased prostate gland tumor incidence ( J:118152 )

♂ • at 140 days of age the incidence of prostate tumors is increased compared to transgenic mice wild-type for Ahr

♂ • at 175 days of age the total number of lymph node metastases is increased but when normalized for the increased number parent tumors no significant difference is seen

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:118152 )

♂ • at 140 days of age the incidence of prostate tumors is increased compared to transgenic mice wild-type for Ahr

♂ • at 175 days of age the total number of lymph node metastases is increased but when normalized for the increased number parent tumors no significant difference is seen