Phenotypes Associated with This Genotype

Genotype
MGI:2654516

• Allelic Composition: Ifngr1^tm1Agt/Ifngr1^tm1Agt
• Genetic Background: involves: 129S7/SvEvBrd

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

Trpm2^tm1.1Alp/Trpm2^tm1.1Alp and Ifngr1^tm1Agt/Ifngr1^tm1Agt mice exhibit increased susceptibility to bacterial infection

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:174397 , J:314959 )

• in mice infected with Listeria monocytogenes (J:174397)

• in T. gondii-infected mice (J:314959)

increased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:115139 )

• MCMV-treated mice exhibit a 5-fold lower LD50 compared with similarly treated wild-type mice

increased susceptibility to induced morbidity/mortality ( J:38363 )

• in MOG35-55-treated mice

immune system

arteritis ( J:115139 )

• chronic in MCMV-infected mice

aortitis ( J:115139 )

• chronic in MCMV-infected mice

abnormal uterine NK cell morphology ( J:56503 )

♀ • the golgi apparatus is poorly developed, the rough ER is disorganized, and numerous mitochondria are seen in uNK cell at implantation sites at gestational day 12

increased uterine NK cell number ( J:56503 )

♀ • after day 10 of gestation increased numbers of uNK cells are found around the metrial gland compared to wild-type controls

abnormal immunoglobulin level ( J:38363 , J:101427 )

• the ratio of IgG1 to IgG2a is increased in MOG35-55-treated mice compared to in similarly treated wild-type mice (J:38363)

• levels of IgG2a and IgG2b neutralizing antibodies are reduced relative to controls after secondary infection with Ectromelia virus (J:101427)

decreased IgG2a level ( J:38363 )

• in MOG35-55-treated mice

abnormal uterine NK cell physiology ( J:56503 )

♀ • decrease in the number of apoptotic uNK cells in the metrial gland afte day 10 of gestation

♀ • uNK cells at implantation sites fail to become heavily granulated and have poorly developed golgi apparati

increased circulating interferon-gamma level ( J:314959 )

• in T. gondii-infected mice

increased circulating interleukin-1 beta level ( J:314959 )

• in T. gondii-infected mice

increased circulating interleukin-6 level ( J:174397 )

• in mice infected with Listeria monocytogenes

decreased circulating tumor necrosis factor level ( J:17878 )

• 10-fold in mice treated with LPS and D-GalN

increased interferon-gamma secretion ( J:38363 )

• in the spleen cells of MOG35-55-treated mice

increased tumor necrosis factor secretion ( J:38363 )

• in the spleen cells of MOG35-55-treated mice

increased susceptibility to experimental autoimmune encephalomyelitis ( J:38363 )

• including increased mortality, spleen cell proliferation, spleen cell levels of IFN-gamma and TNF, and IgG1 to IgG2a ratio following treatment with MOG35-55

decreased susceptibility to endotoxin shock ( J:17878 )

• mice tolerate up to 100 ug of LPS without demonstrating clinical symptoms unlike wild-type mice

• LPS-treated mice exhibit a faster recovery of total leukocyte counts compared with similarly treated wild-type mice

• mice treated with LPS and D-GalN exhibit resistance to endotoxic shock, including reduced serum TNF levels (10-fold) and hepatocellular necrosis, compared with similarly treated wild-type mice

abnormal response to infection ( J:115139 )

• MCMV-infected mice develop chronic arteritis/aortitis, chronic productive infection, and reactivation of latency in spleen and lung explants unlike similarly treated wild-type mice

increased susceptibility to bacterial infection ( J:174397 , J:314959 )

• mice infected with Listeria monocytogenes (Lm) exhibit decreased survival, increased bacterial burden in the spleen and liver, increased IL6 serum levels, and increased numbers of inflammatory abscesses in the liver with parenchyma destruction and necrosis in perivascular regions compared with similarly treated wild-type mice (J:174397)

• T. gondii-infected mice exhibit increased parasite burden in the spleen, liver, and lung, and increased IFN-gamma and IL1b compared with wild-type mice (J:314959)

increased susceptibility to bacterial infection induced morbidity/mortality ( J:174397 , J:314959 )

• in mice infected with Listeria monocytogenes (J:174397)

• in T. gondii-infected mice (J:314959)

increased susceptibility to parasitic infection ( J:114203 )

• T. gondii-exposed mice exhibit increased bacterial load, decreased activation of cerebral blood vessel endothelial cells, and reduced microglial activation compared with similarly treated wild-type mice

• however, recruitment and intracerebral cell movement is normal in T. gondii-exposed mice

increased susceptibility to Herpesvirales infection ( J:81243 )

• slightly more susceptible to MCMV viral infection than controls

increased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:115139 )

• MCMV-treated mice exhibit a 5-fold lower LD50 compared with similarly treated wild-type mice

increased susceptibility to Poxviridae infection ( J:101427 )

• increased susceptibility to Ectromelia virus

• 100% mortality by day 6-12 after primary infection infection

• elevated virus titers in all organs tested after primary infection but much improved after secondary infections

• survive secondary infections

reproductive system

abnormal uterine NK cell physiology ( J:56503 )

♀ • decrease in the number of apoptotic uNK cells in the metrial gland afte day 10 of gestation

♀ • uNK cells at implantation sites fail to become heavily granulated and have poorly developed golgi apparati

abnormal uterus morphology ( J:56503 )

♀ • metrial glands are enlarged compared to wild-type controls

abnormal maternal decidual layer morphology ( J:56503 )

♀ • after gestational day 10 the entire mesometrial decidua becomes progressively necrotic

♀ • by gestational day 14 only a thin layer of tissue remains

abnormal uterine NK cell morphology ( J:56503 )

♀ • the golgi apparatus is poorly developed, the rough ER is disorganized, and numerous mitochondria are seen in uNK cell at implantation sites at gestational day 12

increased uterine NK cell number ( J:56503 )

♀ • after day 10 of gestation increased numbers of uNK cells are found around the metrial gland compared to wild-type controls

liver/biliary system

increased hepatocyte proliferation ( J:38363 )

• in the spleen cells of MOG35-55-treated mice

liver abscess ( J:174397 )

• greater in mice infected with Listeria monocytogenes than in similarly treated wild-type mice

cardiovascular system

abnormal tumor vascularization ( J:63089 )

• mice fail to reject transplanted tumor cells originating from Ifngr1^tm1Agt homozygotes or prevent blood vessel formation into the tumor mass unlike similarly treated wild-type mice

• however, T cell responses to the tumors are normal

abnormal vascular endothelial cell physiology ( J:114203 )

• T. gondii-exposed mice exhibit decreased activation of cerebral blood vessel endothelial cells compared with similarly treated wild-type mice

• however, recruitment and intracerebral cell movement is normal in T. gondii-exposed mice

arteritis ( J:115139 )

• chronic in MCMV-infected mice

aortitis ( J:115139 )

• chronic in MCMV-infected mice

neoplasm

abnormal tumor vascularization ( J:63089 )

• mice fail to reject transplanted tumor cells originating from Ifngr1^tm1Agt homozygotes or prevent blood vessel formation into the tumor mass unlike similarly treated wild-type mice

• however, T cell responses to the tumors are normal

abnormal tumor susceptibility ( J:63089 )

• mice fail to prevent blood vessel formation into tumor masses from tumor cells originating from Ifngr1^tm1Agt homozygotes unlike similarly treated wild-type mice

embryo

abnormal maternal decidual layer morphology ( J:56503 )

♀ • after gestational day 10 the entire mesometrial decidua becomes progressively necrotic

♀ • by gestational day 14 only a thin layer of tissue remains

abnormal uterine NK cell morphology ( J:56503 )

♀ • the golgi apparatus is poorly developed, the rough ER is disorganized, and numerous mitochondria are seen in uNK cell at implantation sites at gestational day 12

increased uterine NK cell number ( J:56503 )

♀ • after day 10 of gestation increased numbers of uNK cells are found around the metrial gland compared to wild-type controls

hematopoietic system

abnormal uterine NK cell morphology ( J:56503 )

♀ • the golgi apparatus is poorly developed, the rough ER is disorganized, and numerous mitochondria are seen in uNK cell at implantation sites at gestational day 12

increased uterine NK cell number ( J:56503 )

♀ • after day 10 of gestation increased numbers of uNK cells are found around the metrial gland compared to wild-type controls

abnormal immunoglobulin level ( J:38363 , J:101427 )

• the ratio of IgG1 to IgG2a is increased in MOG35-55-treated mice compared to in similarly treated wild-type mice (J:38363)

• levels of IgG2a and IgG2b neutralizing antibodies are reduced relative to controls after secondary infection with Ectromelia virus (J:101427)

decreased IgG2a level ( J:38363 )

• in MOG35-55-treated mice

abnormal uterine NK cell physiology ( J:56503 )

♀ • decrease in the number of apoptotic uNK cells in the metrial gland afte day 10 of gestation

♀ • uNK cells at implantation sites fail to become heavily granulated and have poorly developed golgi apparati

homeostasis/metabolism

increased circulating interferon-gamma level ( J:314959 )

• in T. gondii-infected mice

increased circulating interleukin-1 beta level ( J:314959 )

• in T. gondii-infected mice

increased circulating interleukin-6 level ( J:174397 )

• in mice infected with Listeria monocytogenes

decreased circulating tumor necrosis factor level ( J:17878 )

• 10-fold in mice treated with LPS and D-GalN

cellular

increased hepatocyte proliferation ( J:38363 )

• in the spleen cells of MOG35-55-treated mice

endocrine/exocrine glands

abnormal uterine NK cell morphology ( J:56503 )

♀ • the golgi apparatus is poorly developed, the rough ER is disorganized, and numerous mitochondria are seen in uNK cell at implantation sites at gestational day 12

increased uterine NK cell number ( J:56503 )

♀ • after day 10 of gestation increased numbers of uNK cells are found around the metrial gland compared to wild-type controls