Phenotypes Associated with This Genotype

Genotype
MGI:3656133

• Allelic Composition: Cyp1a1^tm1.1Dwn/Cyp1a1^tm1.1Dwn
• Genetic Background: B6.129P2-Cyp1a1^tm1.1Dwn

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

Dioxin-induced hepatic injury in Cyp1a1^tm1.1Dwn/Cyp1a1^tm1.1Dwn and Cyp1a2^tm1Dwn/Cyp1a2^tm1Dwn mice

mortality/aging

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:89337 )

• all male and female mutants survive after being given a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (200 ug/kg), while all male but no female wild-type mice died by 22 - 26 days after exposure

homeostasis/metabolism

increased circulating alanine transaminase level ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

increased circulating aspartate transaminase level ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:89337 )

• all male and female mutants survive after being given a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (200 ug/kg), while all male but no female wild-type mice died by 22 - 26 days after exposure

decreased physiological sensitivity to xenobiotic ( J:89337 )

• TCDD-induced wasting is not seen in homozygotes while thymic involution, decrease in spleen weight, increase in hepatocyte size, increase in hepatic uroporphyrin content, and increase in intra-hepatocyte and total liver lipid are less severe than in TCDD treated wild-type mice

• the ratio of TCDD-induced extrahepatic versus hepatic damage (measured by the ratio of plasma AST to ALT) is less than 1 in homozygotes and greater than 1 in wild-type mice

• however, the distribution of TCDD (liver/adipose ratio) is similar to wild-type mice

increased physiological sensitivity to xenobiotic ( J:147150 , J:163973 )

• after dioxin treatment (64 ug/kg) mice show increased levels of liver inflammation and serum ALT (J:147150)

• however, levels of hydropic degeneration are similar to controls (J:147150)

• benzo[a]pyrene (BaP)-treated mice exhibit moderate toxicity (weight loss, decreased spleen and thymus weight, increased liver weight, increased serum alanine and aspartate transaminase levels, decreased hematocrit and hemoglobin, increased methemoglobin, increased neutrophils, and decreased lymphocytes) compared with similarly treated wild-type mice (J:163973)

• BaP-toxicity is more severe than in similarly treated Cyp1a1^tm4.1Dwn homozygotes (J:163973)

abnormal xenobiotic pharmacokinetics ( J:163973 )

• benzo[a]pyrene (BaP)-treated mice exhibit an 25-fold increase in BaP serum levels compared to wild-type mice

hematopoietic system

decreased thymus weight ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

decreased hematocrit ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

abnormal hemoglobin content ( J:163973 )

• benzo[a]pyrene (BaP)-treated mice exhibit an increase in methemoglobin compared with similarly treated wild-type mice

increased hemoglobin content ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

increased neutrophil cell number ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

decreased lymphocyte cell number ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

decreased spleen weight ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

liver/biliary system

increased liver weight ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

abnormal liver physiology ( J:88957 )

• basal and TCDD-induced NADPH-dependent H2O2 production in hepatic microsomes are decreased compared to wild-type mice

growth/size/body

increased susceptibility to weight loss ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

increased liver weight ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

immune system

decreased thymus weight ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

increased neutrophil cell number ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

decreased lymphocyte cell number ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

decreased spleen weight ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice

endocrine/exocrine glands

decreased thymus weight ( J:163973 )

• in benzo[a]pyrene (BaP)-treated mice