Phenotypes associated with this allele

• Allele Symbol: Ahr^tm1Gonz
• Allele Name: targeted mutation 1, Frank J Gonzales
• Allele ID: MGI:2151800
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ahr^tm1Gonz/Ahr^tm1Gonz	involves: 129S4/SvJae	MGI:3656138
hm2	Ahr^tm1Gonz/Ahr^tm1Gonz	involves: 129S4/SvJae * C57BL/6J	MGI:3776525
hm3	Ahr^tm1Gonz/Ahr^tm1Gonz	involves: 129S4/SvJae * C57BL/6N	MGI:2450836

Genotype
MGI:3656138

hm1

• Allelic Composition: Ahr^tm1Gonz/Ahr^tm1Gonz
• Genetic Background: involves: 129S4/SvJae

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

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:36360 )

• interperitoneal injection of 2000 ug/kg TCDD fails to induce thymic cortical atrophy, changes in thymic lymphocyte numbers, increased hepatic lipid accumulation, or increases in liver weight all of which are seen in wild-type and heterozygous mice injected with 200 ug/kg TCDD

• interperitoneal injection of 2000 ug/kg TCDD but not 200 ug/kg does induce a significant increase in lymphocyte and marcophage infiltrates and perivascular cuffs in the lung which are seen in wild-type and heterozygous mice exposed to200 ug/kg TCDD

reproductive system

reproductive system phenotype ( J:76280 )

N • mammary gland development is normal

Genotype
MGI:3776525

hm2

• Allelic Composition: Ahr^tm1Gonz/Ahr^tm1Gonz
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

mortality/aging

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:113285 )

• unlike C57BL/6-Ahr^b-1 neonates, mice are not susceptible to lethality induced by in utero exposure to cHBB

reproductive system

decreased litter size ( J:113285 )

• mice produce smaller litters than wild-type mice

• however, exposure to cHBB does not further decrease fecundity

homeostasis/metabolism

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:113285 )

• unlike C57BL/6-Ahr^b-1 neonates, mice are not susceptible to lethality induced by in utero exposure to cHBB

decreased physiological sensitivity to xenobiotic ( J:113285 )

• unlike C57BL/6-Ahr^b-1 neonates, mice are not susceptible to lethality induced by in utero exposure to cHBB

Genotype
MGI:2450836

hm3

• Allelic Composition: Ahr^tm1Gonz/Ahr^tm1Gonz
• Genetic Background: involves: 129S4/SvJae * C57BL/6N

mortality/aging

premature death ( J:44690 )

• over 20% are moribund by around 10 - 12 months of age

postnatal lethality, incomplete penetrance ( J:25048 )

• about 40% - 50% of pups die within 1 - 4 days of birth

homeostasis/metabolism

abnormal thrombosis ( J:44690 )

• seen in ecchymotic areas of the uterus in retired breeders

abnormal atrial thrombosis ( J:44690 )

• at 10 month of age, 3 of 52 have mural thrombi of the atrium with marked fibrosis of the adjacent myocardium

decreased physiological sensitivity to xenobiotic ( J:25048 )

• injection of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 40 ug/kg fails to increase expression of Cyp1a1, Cyp1a2, or Ugt1a6a

reproductive system

abnormal uterus morphology ( J:44690 )

♀ • in 12 retired breeders ecchymotic areas are seen on the serosa and are identified histologically by hypertrophy, thromboses, and mineralization of the serosal vessels

reduced female fertility ( J:44690 )

♀ • after 3 - 4 cycles females have trouble maintaining pregnancies

decreased litter size ( J:44690 )

• coincident with development of uterine lesions

immune system

abnormal spleen morphology ( J:44690 )

enlarged spleen ( J:44690 )

• in about 80% of mice reduced T- and B-cell area is accompanied by mild to moderate splenomegaly

abnormal spleen red pulp morphology ( J:44690 )

• myeloid hyperplasia of the red pulp is seen in mice with mild to moderate splenomegaly

small spleen ( J:25048 )

• at 4 weeks of age; however, spleen architecture is similar to wild-type

spleen hypoplasia ( J:25048 )

• at 2 - 3 weeks of age, spleens contain 75 - 85% fewer lymphocytes; however the number of lymphocytes is similar to wild-type by 10 - 12 weeks of age

• at 25 - 32 weeks of age, lymphocyte numbers are about 50% of wild-type

• however, the proportion of B and T cells is similar to wild-type and thymus cellularity is similar to wild-type

decreased spleen white pulp amount ( J:44690 )

• significant decrease in the size of the T- and B-cell zones and in the number of T- and B-cells in the spleen

increased inflammatory response ( J:25048 )

• in pups that die postnatally lymphocyte infiltration is seen in many organs, particularly in the gut, urinary tract, and lung

heart inflammation ( J:44690 )

• at 10 month of age, 25% of hearts display chronic, focal inflammation in the myocardium of the ventricles or atrium

colitis ( J:44690 )

• in some cases of rectal prolapse colonic hyperplasia and severe inflammation are also seen

• in mice with prolapse many helical bacteria are present in the crypts and significant titers of antibodies against Helicobacter hepaticus are detected

bile duct inflammation ( J:25048 )

• mild to moderate inflammation is seen in some homozygotes

folliculitis ( J:44690 )

• ruptured follicles are associated with a mixed inflammatory cell infiltrate

liver/biliary system

bile duct inflammation ( J:25048 )

• mild to moderate inflammation is seen in some homozygotes

abnormal liver morphology ( J:25048 , J:44690 )

• centrilobular hypercellularity (J:25048)

• hepatic portal vascular lesions characterized by increased numbers of arteries and arterioles (J:44690)

• however, Heliobacter hepaticus hepatitis is not seen (J:44690)

abnormal hepatocyte morphology ( J:25048 , J:44690 )

• eosinophilia is seen in periportal hepatocytes (J:25048)

• hepatocytomegalic periportal hepatocytes with eosinophilic cytoplasm (J:44690)

decreased liver weight ( J:25048 )

• a 4 weeks of age, liver weight is 2.9 +/- 0.3% of body weight compared to 6.1 +/- 0.4% in wild-type mice

increased hepatoma incidence ( J:44690 )

• seen in 1 of 12 mice at 11-13 months of age

increased liver adenoma incidence ( J:44690 )

• seen in 3 of 12 mice at 11-13 months of age

liver fibrosis ( J:25048 , J:44690 )

• pronounced fibrosis of the portal tract, visible at 3 weeks of age (J:25048)

• minimal to mild portal fibrosis (J:44690)

abnormal liver physiology ( J:25048 )

• constitutive expression of Cyp1a2 and Ugt1a6a are decreased by 90 +/- 5% and 85 +/- 5%, respectively, relative to wild-type mice

• liver glycogen depletion

growth/size/body

enlarged heart ( J:44690 )

• seen around 9 months of age

increased heart weight ( J:44690 )

• at 10 months of age, heart weight is increased to 0.8 +/- 0.13% of body weight compared to 0.47 +/- 0.06% in wild-type mice

weight loss ( J:44690 )

• a 15 - 20% weight loss is seen in over 20% of mice by around 10 - 12 months of age

postnatal growth retardation ( J:25048 )

• slower growth rate within the first 2 - 4 weeks of life

enlarged spleen ( J:44690 )

• in about 80% of mice reduced T- and B-cell area is accompanied by mild to moderate splenomegaly

digestive/alimentary system

chronic diarrhea ( J:44690 )

• seen in several homozygotes

abnormal colon morphology ( J:44690 )

• in some cases of rectal prolapse colonic hyperplasia and severe inflammation are also seen

rectal prolapse ( J:44690 )

• at 6 - 13 months of age, 48% develop rectal prolapse

• in mice over 9 months of age, prolapse is characterized by marked epithelial hyperplasia and mucus secretion in the submucosa

• in mice with prolapse many helical bacteria are present in the crypts and significant titers of antibodies against Helicobacter hepaticus are detected; however prolapse has been seen in mice from 4 different animal facilities and mice with and without prolapse are seen in the same cage when housed in groups

abnormal stomach pyloric region morphology ( J:44690 )

• pyloric regions of the glandular stomach display focal, proliferative lesions with the highest incidence in mice over 9 months of age

• lesions start as focal hyperplasia and progress to large plaques or polyps

gastric polyps ( J:44690 )

• lesions in the pyloric region of the glandular stomach start as focal hyperplasia and progress to large plaques or polyps

colitis ( J:44690 )

• in some cases of rectal prolapse colonic hyperplasia and severe inflammation are also seen

• in mice with prolapse many helical bacteria are present in the crypts and significant titers of antibodies against Helicobacter hepaticus are detected

cardiovascular system

abnormal blood vessel morphology ( J:44690 )

• mineralization of the serosal vessels in ecchymotic areas of the uterus

• hepatic portal vascular lesions characterized by increased numbers of arteries and arterioles

vascular smooth muscle hypertrophy ( J:44690 )

• at 10 month of age, almost 10% have enlarged coronary arteries and arterioles due to smooth muscle hypertrophy

abnormal heart morphology ( J:44690 )

abnormal coronary artery morphology ( J:44690 )

• at 10 month of age, almost 10% have enlarged coronary arteries and arterioles due to smooth muscle hypertrophy

enlarged heart ( J:44690 )

• seen around 9 months of age

increased heart weight ( J:44690 )

• at 10 months of age, heart weight is increased to 0.8 +/- 0.13% of body weight compared to 0.47 +/- 0.06% in wild-type mice

cardiac fibrosis ( J:44690 )

• at 10 month of age, 25% of hearts display fibrosis in the myocardium of the ventricles or atrium

heart inflammation ( J:44690 )

• at 10 month of age, 25% of hearts display chronic, focal inflammation in the myocardium of the ventricles or atrium

neoplasm

increased hepatoma incidence ( J:44690 )

• seen in 1 of 12 mice at 11-13 months of age

increased liver adenoma incidence ( J:44690 )

• seen in 3 of 12 mice at 11-13 months of age

hematopoietic system

abnormal spleen morphology ( J:44690 )

enlarged spleen ( J:44690 )

• in about 80% of mice reduced T- and B-cell area is accompanied by mild to moderate splenomegaly

abnormal spleen red pulp morphology ( J:44690 )

• myeloid hyperplasia of the red pulp is seen in mice with mild to moderate splenomegaly

small spleen ( J:25048 )

• at 4 weeks of age; however, spleen architecture is similar to wild-type

spleen hypoplasia ( J:25048 )

• at 2 - 3 weeks of age, spleens contain 75 - 85% fewer lymphocytes; however the number of lymphocytes is similar to wild-type by 10 - 12 weeks of age

• at 25 - 32 weeks of age, lymphocyte numbers are about 50% of wild-type

• however, the proportion of B and T cells is similar to wild-type and thymus cellularity is similar to wild-type

decreased spleen white pulp amount ( J:44690 )

• significant decrease in the size of the T- and B-cell zones and in the number of T- and B-cells in the spleen

muscle

vascular smooth muscle hypertrophy ( J:44690 )

• at 10 month of age, almost 10% have enlarged coronary arteries and arterioles due to smooth muscle hypertrophy

integument

abnormal coat/ hair morphology ( J:44690 )

abnormal auchene hair morphology ( J:44690 )

• make up 25 - 50% of plucked truncal pelage hairs rather than 10% as in wild-type mice

• hair fibers have worn rounded edges, worn cuticular scales, and some areas with small surface blebs with folding and breaking at the fold sites

alopecia ( J:44690 )

• skin lesions usually begin with alopecia

abnormal hair shaft morphology ( J:44690 )

• dystrophic follicles may have an abnormal hair fiber

abnormal hair follicle morphology ( J:44690 )

• follicles are widely separated and dystrophic

• dystrophic follicles are empty, markedly dilated at the piliary canal and have either a structurally abnormal hair fiber or are ruptured

folliculitis ( J:44690 )

• ruptured follicles are associated with a mixed inflammatory cell infiltrate

dilated piliary canal ( J:44690 )

• dilation of the piliary canal

abnormal epidermal layer morphology ( J:44690 )

hypergranulosis ( J:44690 )

• hypergranulosis is associated with the healing of skin ulcers

acanthosis ( J:44690 )

• mild to moderate acanthosis is associated with the healing of skin ulcers

scaly skin ( J:44690 )

• at 6 - 13 months of age, 53% develop dorsal, localized, thick, scaly skin

skin lesions ( J:44690 )

• progressive focal lesions are seen on the dorsal skin and in some mice extend to the ears and lateral aspects of the abdomen

• dermal mastocytosis is common in areas of inflamed skin

spontaneous skin ulceration ( J:44690 )

• skin lesions progress from alopecia to ulcers of variable severity

• ulcers heal by lateral hyperplasia of the intact epithelium with dermal scarring

abnormal skin condition ( J:44690 )

thick skin ( J:44690 )

• at 6 - 13 months of age, 53% develop dorsal, localized, thick, scaly skin