All Phenotypes Il18<tm1Aki> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Il18^tm1Aki/Il18^tm1Aki	B6.129P2-Il18^tm1Aki	MGI:3789028
hm2	Il18^tm1Aki/Il18^tm1Aki	C.129P2-Il18^tm1Aki	MGI:3789016
hm3	Il18^tm1Aki/Il18^tm1Aki	involves: 129P2/OlaHsd	MGI:3784500
hm4	Il18^tm1Aki/Il18^tm1Aki	involves: 129P2/OlaHsd * C57BL/6	MGI:3785864
ht5	Il18^tm1Aki/Il18⁺	involves: 129P2/OlaHsd	MGI:3785896
cx6	Il12b^tm1Jm/Il12b^tm1Jm Il18^tm1Aki/Il18^tm1Aki	involves: 129P2/OlaHsd * 129S1/SvImJ	MGI:3784501
cx7	Il18^tm1Aki/Il18^tm1Aki Il1b^tm1Dch/Il1b^tm1Dch	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:3851238
cx8	Il18^tm1Aki/Il18^tm1Aki Nlrp1a^Neut1/Nlrp1a^Neut1	involves: 129P2/OlaHsd * C57BL/6	MGI:5474287
cx9	Il18^tm1Aki/Il18^tm1Aki Tg(KRT14-CASP1)1Miz/0	involves: 129P2/OlaHsd * C57BL/6	MGI:5563689

Allelic Composition	Il18^tm1Aki/Il18^tm1Aki
Genetic Background	B6.129P2-Il18^tm1Aki

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il18^tm1Aki mutation (3 available); any Il18 mutation (29 available)

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

immune system

impaired neutrophil chemotaxis ( J:125285 )

• less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae

increased susceptibility to induced colitis ( J:173245 )

• mice exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis compared with similarly treated wild-type mice

• mice transmit increased susceptibility to DSS-induced colitis to co-housed wild-type mice

increased susceptibility to bacterial infection ( J:125285 )

• bacterial counts in the lung are 20-fold higher one day after infection with Haemophilus influenzae

• there is less inflammation present in the lungs 6- and 24- hours after infection with histological scores significantly reduced compared to wild-type mice

• mice are able to clear infection from the lungs 10 days after infection, which is similar to wild-type mice

digestive/alimentary system

abnormal gut flora balance ( J:173245 )

• mice and co-housed wild-type mice exhibit expanded bacterial phylotypes compared with wild-type mice

increased susceptibility to induced colitis ( J:173245 )

• mice exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis compared with similarly treated wild-type mice

• mice transmit increased susceptibility to DSS-induced colitis to co-housed wild-type mice

cellular

impaired neutrophil chemotaxis ( J:125285 )

• less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae

hematopoietic system

impaired neutrophil chemotaxis ( J:125285 )

• less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae

Allelic Composition	Il18^tm1Aki/Il18^tm1Aki
Genetic Background	C.129P2-Il18^tm1Aki

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il18^tm1Aki mutation (3 available); any Il18 mutation (29 available)

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

digestive/alimentary system

gastrointestinal hemorrhage ( J:120594 )

• there is less bleeding associated with stress-induced ulcers in the stomach with bleeding index scores being about half that of wild-type mice

hyperchlorhydria ( J:120594 )

• there is decreased secretion of gastric acid in the stomach 1- and 2- hours after stress induction compared to wild-type mice

stomach inflammation ( J:120594 )

• histidine decarboxylase activity in the stomachof untreated mice is significantly lower than in wild-type mice

• histamine concentrations in the gastric mucosa 1- and 2- hours after stress induction are 2-fold lower than in wild-type mice

cardiovascular system

gastrointestinal hemorrhage ( J:120594 )

• there is less bleeding associated with stress-induced ulcers in the stomach with bleeding index scores being about half that of wild-type mice

immune system

stomach inflammation ( J:120594 )

• histidine decarboxylase activity in the stomachof untreated mice is significantly lower than in wild-type mice

• histamine concentrations in the gastric mucosa 1- and 2- hours after stress induction are 2-fold lower than in wild-type mice

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

immune system

impaired natural killer cell mediated cytotoxicity ( J:46514 )

• the killing activity of splenic NK cells is about 1/3^rd that of wild-type mice as measured by in vitro co-culturing with YAC-1 target cells

• normal level of target cell killing can be restored by in vivo administration of IL-18 for two days

• target cell killing can also be restored by in vivo pre-treatment with high amounts of IL-12 or the addition of small amounts of IL-12 to the co-culture

abnormal T-helper 1 physiology ( J:46514 )

• in vivo Th1 cell response is impaired as indicated by the low amounts of IFN-gamma produced by T cells in response to P. acnes or M. bovis antigens

• in vitro differentiation of Th1 T cells by culturing in the presence of IL-12 is normal

abnormal macrophage physiology ( J:112400 )

• macrophages are resistant to cytotoxicity by SP1^- Salmonella

decreased circulating interferon-gamma level ( J:46514 )

• serum IFN-gamma levels are 1/5^th of wild-type levels 6 hours after treatment with LPS in mice sensitized to Prionibacterium acnes (P. acnes)

decreased circulating interleukin-18 level ( J:46514 , J:122588 )

• IL-18 is absent in the serum before and after LPS injection (J:46514)

• IL-18 was undetectable in the sera of mice (J:122588)

decreased interferon-gamma secretion ( J:46514 )

• splenic T cells produce about 1/10^th the amount of IFN-gamma as T cells from wild-type mice 7 days after injection with heat killed P. acnes

increased susceptibility to bacterial infection ( J:112400 )

• mice succumb more rapidly than controls to 10⁸ CFU of Salmonella with a median survival time of 6 days compared to 8 days for controls

• there is an average 30-fold-higher bacterial loads in infected Peyer's patches, mesenteric lymph nodes, and spleens than in the infected organs of wild-type animals

growth/size/body

increased susceptibility to age related obesity ( J:122588 )

• female mice have a greater body weight gain during the 5^th month of life than controls going from 1% greater mean body weight at 4 months of age to 27% greater mean body weight at 5 months of age

• male mice have a 2-fold greater weight gain between 4 and 7 months of age with mean body weight being 14% higher by 27 weeks of age compared to controls

adipose tissue

increased white adipose tissue amount ( J:122588 )

• the collective white fat pad mass of these mice is 2-3 fold greater that of wild-type mice

increased total fat pad weight ( J:122588 )

• white fat pads are heavier on both absolute and relative scales with the largest increases occurring in the inguinal and gonadal pads where weights were 1 gram larger compared to controls

increased percent body fat/body weight ( J:122588 )

• weight gain is mostly due to increases in white fat resulting in a percent body fats that exceed 20% for mice 30 weeks in age

homeostasis/metabolism

decreased circulating interferon-gamma level ( J:46514 )

• serum IFN-gamma levels are 1/5^th of wild-type levels 6 hours after treatment with LPS in mice sensitized to Prionibacterium acnes (P. acnes)

decreased circulating interleukin-18 level ( J:46514 , J:122588 )

• IL-18 is absent in the serum before and after LPS injection (J:46514)

• IL-18 was undetectable in the sera of mice (J:122588)

decreased energy expenditure ( J:122588 )

• mice gain 2- to 3-fold more body weight than controls per unit body weight consumed

• female mice have stably reduced oxygen consumption along with decreased carbon dioxide and heat production

decreased oxygen consumption ( J:122588 )

• female mice have stably reduced oxygen consumption along with decreased carbon dioxide

• the respiratory exchange ratio (VCO-2/ VO-2) is increased in both female and male mice early in the dark cycle

behavior/neurological

polyphagia ( J:122588 )

• hyperphagia is seen at 15 weeks of age before changes in body weight are observed

• overeating of chow increases later in adulthood for both female and male mice even when comsumption is normalized to bodyweight

• hyperphagia varied according to the time of day with increase consumption occurring during the last six hours of the dark cycle and the first three hours of the light cycle

• during this period of the daily cycle mice will eat twice as much as controls

• hyperphagia also occurs on a low fat diet but not on a high fat diet when consumption is normalized to bodyweight

hematopoietic system

impaired natural killer cell mediated cytotoxicity ( J:46514 )

• the killing activity of splenic NK cells is about 1/3^rd that of wild-type mice as measured by in vitro co-culturing with YAC-1 target cells

• normal level of target cell killing can be restored by in vivo administration of IL-18 for two days

• target cell killing can also be restored by in vivo pre-treatment with high amounts of IL-12 or the addition of small amounts of IL-12 to the co-culture

abnormal T-helper 1 physiology ( J:46514 )

• in vivo Th1 cell response is impaired as indicated by the low amounts of IFN-gamma produced by T cells in response to P. acnes or M. bovis antigens

• in vitro differentiation of Th1 T cells by culturing in the presence of IL-12 is normal

abnormal macrophage physiology ( J:112400 )

• macrophages are resistant to cytotoxicity by SP1^- Salmonella

Allelic Composition	Il18^tm1Aki/Il18^tm1Aki
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il18^tm1Aki mutation (3 available); any Il18 mutation (29 available)

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

vision/eye

abnormal retina vasculature morphology ( J:92254 )

• mice 7 days of age display angiectasis and vascular leakage in the mid-periphery of the retina

• mice 14 days of age have areas of the retina that are not perfused with capillaries

• abnormal blood vessels are found in the vitreous outside of the inner-limiting membrane in young mice

• other blood vessels in the retina of young mice have a tortured appearance

• vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age

retina hemorrhage ( J:92254 )

• vascular leakage is observed in the retinas of mice starting at 7 days of age

• vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age

cardiovascular system

abnormal retina vasculature morphology ( J:92254 )

• mice 7 days of age display angiectasis and vascular leakage in the mid-periphery of the retina

• mice 14 days of age have areas of the retina that are not perfused with capillaries

• abnormal blood vessels are found in the vitreous outside of the inner-limiting membrane in young mice

• other blood vessels in the retina of young mice have a tortured appearance

• vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age

abnormal heart left ventricle morphology ( J:118183 )

• the left ventricular volume of 3-4 month old mice is reduced

• hypertrophic growth of the left ventricle induced by pressure overload is significantly reduced compared to wild-type controls

• end diastolic volumes increased in response to pressure overload compared to wild-type mice that have decreased diastolic volumes

retina hemorrhage ( J:92254 )

• vascular leakage is observed in the retinas of mice starting at 7 days of age

• vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age

decreased ventricle muscle contractility ( J:118183 )

• left ventricle contractility decreased in response to pressure overload compared to the increases observed in wild-type mice

hematopoietic system

abnormal microglial cell morphology ( J:122031 )

• stress-induced increase in microglial cell surface, which is a marker of activation, is significantly reduced by 1.5 to 3 fold in these mice

immune system

abnormal microglial cell morphology ( J:122031 )

• stress-induced increase in microglial cell surface, which is a marker of activation, is significantly reduced by 1.5 to 3 fold in these mice

nervous system

abnormal microglial cell morphology ( J:122031 )

• stress-induced increase in microglial cell surface, which is a marker of activation, is significantly reduced by 1.5 to 3 fold in these mice

decreased cerebral infarct size ( J:124249 )

• the total volume of infarction caused by hypoxia-ischemia (HI) was reduced from 53% in wild-type mice to 42% in these mice

• the neuropathological scores to measure brain injury resulting from HI were reduced with the most marked reduction of 35% occurring in the cerebral cortex

homeostasis/metabolism

decreased cerebral infarct size ( J:124249 )

• the total volume of infarction caused by hypoxia-ischemia (HI) was reduced from 53% in wild-type mice to 42% in these mice

• the neuropathological scores to measure brain injury resulting from HI were reduced with the most marked reduction of 35% occurring in the cerebral cortex

muscle

decreased ventricle muscle contractility ( J:118183 )

• left ventricle contractility decreased in response to pressure overload compared to the increases observed in wild-type mice

Allelic Composition	Il18^tm1Aki/Il18⁺
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il18^tm1Aki mutation (3 available); any Il18 mutation (29 available)

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

behavior/neurological

polyphagia ( J:122588 )

• female mice overeat chow relative to wild-type mice during the last 6 hours of night and the first three hours in the day but not to the degree observed in Il18^tm1Aki homozygotes

Allelic Composition	Il12b^tm1Jm/Il12b^tm1Jm Il18^tm1Aki/Il18^tm1Aki
Genetic Background	involves: 129P2/OlaHsd * 129S1/SvImJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il12b^tm1Jm mutation (4 available); any Il12b mutation (31 available)
Il18^tm1Aki mutation (3 available); any Il18 mutation (29 available)

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

immune system

impaired natural killer cell mediated cytotoxicity ( J:46514 )

• the killing ability of splenic NK cells is severely impaired with significantly less activity occurring than NK cells from Il18^tm1Aki or Il12b^tm1Jm homozygotes

abnormal T-helper 1 physiology ( J:46514 )

• in vivo Th1 cell response is impaired as indicated by the low amounts of IFN-gamma produced by T cells in response to M. bovis antigens

decreased interferon-gamma secretion ( J:46514 )

• splenic T cells produce 12-fold lower amounts of IFN-gamma as T cells from wild-type mice 14 days after injection with heat killed M. Bovis

hematopoietic system

impaired natural killer cell mediated cytotoxicity ( J:46514 )

• the killing ability of splenic NK cells is severely impaired with significantly less activity occurring than NK cells from Il18^tm1Aki or Il12b^tm1Jm homozygotes

abnormal T-helper 1 physiology ( J:46514 )

• in vivo Th1 cell response is impaired as indicated by the low amounts of IFN-gamma produced by T cells in response to M. bovis antigens

Allelic Composition	Il18^tm1Aki/Il18^tm1Aki Il1b^tm1Dch/Il1b^tm1Dch
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il18^tm1Aki mutation (3 available); any Il18 mutation (29 available)
Il1b^tm1Dch mutation (1 available); any Il1b mutation (24 available)

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

immune system

increased susceptibility to bacterial infection ( J:112400 )

• mice succumb more rapidly than controls to10⁸ CFU of Salmonella with a median survival time of 6 days compared to 8 days for controls

• there is an average 30-fold-higher bacterial loads in infected Peyer's patches, mesenteric lymph nodes, and spleens than in the infected organs of wild-type animals

Allelic Composition	Il18^tm1Aki/Il18^tm1Aki Nlrp1a^Neut1/Nlrp1a^Neut1
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il18^tm1Aki mutation (3 available); any Il18 mutation (29 available)
Nlrp1a^Neut1 mutation (0 available); any Nlrp1a mutation (64 available)

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

mortality/aging

premature death ( J:191055 )

• succumb to inflammatory disease at 5-10 weeks of age

• normal mortality in a germ free environment

immune system

increased neutrophil cell number ( J:191055 )

• increased blood neutrophils

• no neutrophil infiltration of the liver

• neutrophile numbers are like controls in a germ free environment

abnormal inflammatory response ( J:191055 )

• accelerated onset of inflammatory disease

myocarditis ( J:191055 )

• increased frequency of myocarditis

hematopoietic system

increased neutrophil cell number ( J:191055 )

• increased blood neutrophils

• no neutrophil infiltration of the liver

• neutrophile numbers are like controls in a germ free environment

cardiovascular system

myocarditis ( J:191055 )

• increased frequency of myocarditis

Allelic Composition	Il18^tm1Aki/Il18^tm1Aki Tg(KRT14-CASP1)1Miz/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il18^tm1Aki mutation (3 available); any Il18 mutation (29 available)
Tg(KRT14-CASP1)1Miz mutation (0 available)

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

hematopoietic system

decreased IgE level ( J:78602 )

• low serum IgE levels

decreased IgG1 level ( J:78602 )

• low serum IgG1 levels

immune system

immune system phenotype ( J:78602 )

N	• diminution in the number of cutaneous mast cells and serum histamine levels compared to single Tg(KRT14-CASP1)1Miz mice

decreased IgE level ( J:78602 )

• low serum IgE levels

decreased IgG1 level ( J:78602 )

• low serum IgG1 levels

integument

integument phenotype ( J:78602 )

N	• mice do not exhibit frequent skin scratching nor dermatitis by 6 months of age

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