growth/size/body region phenotype

• increased susceptibility to age related obesity
  • 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
  (MGI Ref ID 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
  (MGI Ref ID J:122588)

hematopoietic system phenotype

• abnormal macrophage physiology
  • macrophages are resistant to cytotoxicity by SP1^- Salmonella
  (MGI Ref ID J:112400)

• abnormal T-helper 1 physiology
  • Normal - in vitro differentiation of Th1 T cells by culturing in the presence of IL-12 is normal
  (MGI Ref ID 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
  (MGI Ref ID J:46514)

• impaired natural killer cell mediated cytotoxicity
  • normal level of target cell killing can be restored by in vivo administration of IL-18 for two days
  (MGI Ref ID J:46514)
  • 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
  (MGI Ref ID 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
  (MGI Ref ID J:46514)

homeostasis/metabolism phenotype

• decreased circulating interleukin-18 level
  • IL-18 was undetectable in the sera of mice
  (MGI Ref ID J:122588)
  • IL-18 is absent in the serum before and after LPS injection
  (MGI Ref ID J:46514)

• decreased energy expenditure
  • female mice have stably reduced oxygen consumption along with decreased carbon dioxide and heat production
  (MGI Ref ID J:122588)
  • mice gain 2- to 3-fold more body weight than controls per unit body weight consumed
  (MGI Ref ID J:122588)

• decreased oxygen consumption
  • the respiratory exchange ratio (VCO-2/ VO-2) is increased in both female and male mice early in the dark cycle
  (MGI Ref ID J:122588)
  • female mice have stably reduced oxygen consumption along with decreased carbon dioxide
  (MGI Ref ID J:122588)

• decreased circulating interferon-gamma level
  • Normal - 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)
  (MGI Ref ID J:46514)

adipose tissue phenotype

• increased total fat pad weight
  • 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
  (MGI Ref ID J:122588)

• increased white adipose tissue amount
  • the collective white fat pad mass of these mice is 2-3 fold greater that of wild-type mice
  (MGI Ref ID J:122588)

• increased percent body fat/body weight
  • 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
  (MGI Ref ID J:122588)

immune system phenotype

• abnormal T-helper 1 physiology
  • 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
  (MGI Ref ID J:46514)
  • Normal - in vitro differentiation of Th1 T cells by culturing in the presence of IL-12 is normal
  (MGI Ref ID J:46514)

• decreased circulating interferon-gamma level
  • Normal - 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)
  (MGI Ref ID J:46514)

• impaired natural killer cell mediated cytotoxicity
  • normal level of target cell killing can be restored by in vivo administration of IL-18 for two days
  (MGI Ref ID 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
  (MGI Ref ID J:46514)
  • 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
  (MGI Ref ID J:46514)

• abnormal macrophage physiology
  • macrophages are resistant to cytotoxicity by SP1^- Salmonella
  (MGI Ref ID J:112400)

• decreased circulating interleukin-18 level
  • IL-18 was undetectable in the sera of mice
  (MGI Ref ID J:122588)
  • IL-18 is absent in the serum before and after LPS injection
  (MGI Ref ID J:46514)

• increased susceptibility to bacterial infection
  • 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
  (MGI Ref ID J:112400)
  • 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
  (MGI Ref ID J:112400)

• decreased interferon-gamma secretion
  • 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
  (MGI Ref ID J:46514)

behavior/neurological phenotype

• polyphagia
  • 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
  (MGI Ref ID J:122588)
  • during this period of the daily cycle mice will eat twice as much as controls
  (MGI Ref ID J:122588)
  • hyperphagia is seen at 15 weeks of age before changes in body weight are observed
  (MGI Ref ID J:122588)
  • hyperphagia also occurs on a low fat diet but not on a high fat diet when consumption is normalized to bodyweight
  (MGI Ref ID J:122588)
  • overeating of chow increases later in adulthood for both female and male mice even when comsumption is normalized to bodyweight
  (MGI Ref ID J:122588)

hematopoietic system phenotype

• abnormal microglial cell morphology
  • 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
  (MGI Ref ID J:122031)

homeostasis/metabolism phenotype

• decreased cerebral infarction size
  • the total volume of infarction caused by hypoxia-ischemia (HI) was reduced from 53% in wild-type mice to 42% in these mice
  (MGI Ref ID J:124249)
  • the neuropathological scores to measure brain injury resulting from HI were reduced with the most marked reduction of 35% occurring in the cerebral cortex
  (MGI Ref ID J:124249)

immune system phenotype

• abnormal microglial cell morphology
  • 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
  (MGI Ref ID J:122031)

muscle phenotype

• decreased ventricle muscle contractility
  • left ventricle contractility decreased in response to pressure overload compared to the increases observed in wild-type mice
  (MGI Ref ID J:118183)

nervous system phenotype

• decreased cerebral infarction size
  • the total volume of infarction caused by hypoxia-ischemia (HI) was reduced from 53% in wild-type mice to 42% in these mice
  (MGI Ref ID J:124249)
  • the neuropathological scores to measure brain injury resulting from HI were reduced with the most marked reduction of 35% occurring in the cerebral cortex
  (MGI Ref ID J:124249)

• abnormal microglial cell morphology
  • 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
  (MGI Ref ID J:122031)

vision/eye phenotype

• abnormal retinal vasculature morphology
  • other blood vessels in the retina of young mice have a tortured appearance
  (MGI Ref ID J:92254)
  • mice 7 days of age display angiectasis and vascular leakage in the mid-periphery of the retina
  (MGI Ref ID J:92254)
  • abnormal blood vessels are found in the vitreous outside of the inner-limiting membrane in young mice
  (MGI Ref ID J:92254)
  • Normal - vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age
  (MGI Ref ID J:92254)
  • mice 14 days of age have areas of the retina that are not perfused with capillaries
  (MGI Ref ID J:92254)

• retinal hemorrhage
  • Normal - vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age
  (MGI Ref ID J:92254)
  • vascular leakage is observed in the retinas of mice starting at 7 days of age
  (MGI Ref ID J:92254)

cardiovascular system phenotype

• abnormal retinal vasculature morphology
  • other blood vessels in the retina of young mice have a tortured appearance
  (MGI Ref ID J:92254)
  • mice 14 days of age have areas of the retina that are not perfused with capillaries
  (MGI Ref ID J:92254)
  • abnormal blood vessels are found in the vitreous outside of the inner-limiting membrane in young mice
  (MGI Ref ID J:92254)
  • Normal - vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age
  (MGI Ref ID J:92254)
  • mice 7 days of age display angiectasis and vascular leakage in the mid-periphery of the retina
  (MGI Ref ID J:92254)

• abnormal heart left ventricle morphology
  • hypertrophic growth of the left ventricle induced by pressure overload is significantly reduced compared to wild-type controls
  (MGI Ref ID J:118183)
  • the left ventricular volume of 3-4 month old mice is reduced
  (MGI Ref ID J:118183)
  • end diastolic volumes increased in response to pressure overload compared to wild-type mice that have decreased diastolic volumes
  (MGI Ref ID J:118183)

• retinal hemorrhage
  • vascular leakage is observed in the retinas of mice starting at 7 days of age
  (MGI Ref ID J:92254)
  • Normal - vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age
  (MGI Ref ID J:92254)

• decreased ventricle muscle contractility
  • left ventricle contractility decreased in response to pressure overload compared to the increases observed in wild-type mice
  (MGI Ref ID J:118183)

cardiovascular system phenotype

• gastrointestinal hemorrhage
  • there is less bleeding associated with stress-induced ulcers in the stomach with bleeding index scores being about half that of wild-type mice
  (MGI Ref ID J:120594)

digestive/alimentary phenotype

• hyperchlorhydria
  • there is decreased secretion of gastric acid in the stomach 1- and 2- hours after stress induction compared to wild-type mice
  (MGI Ref ID J:120594)

• gastrointestinal hemorrhage
  • there is less bleeding associated with stress-induced ulcers in the stomach with bleeding index scores being about half that of wild-type mice
  (MGI Ref ID J:120594)

• stomach inflammation
  • histidine decarboxylase activity in the stomachof untreated mice is significantly lower than in wild-type mice
  (MGI Ref ID J:120594)
  • histamine concentrations in the gastric mucosa 1- and 2- hours after stress induction are 2-fold lower than in wild-type mice
  (MGI Ref ID J:120594)

immune system phenotype

• stomach inflammation
  • histamine concentrations in the gastric mucosa 1- and 2- hours after stress induction are 2-fold lower than in wild-type mice
  (MGI Ref ID J:120594)
  • histidine decarboxylase activity in the stomachof untreated mice is significantly lower than in wild-type mice
  (MGI Ref ID J:120594)

behavior/neurological phenotype

• polyphagia
  • 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
  (MGI Ref ID J:122588)

cellular phenotype

• impaired neutrophil chemotaxis
  • less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae
  (MGI Ref ID J:125285)

digestive/alimentary phenotype

• abnormal gut flora balance
  • mice and co-housed wild-type mice exhibit expanded bacterial phylotypes compared with wild-type mice
  (MGI Ref ID J:173245)

• increased susceptibility to induced colitis
  • mice exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis compared with similarly treated wild-type mice
  (MGI Ref ID J:173245)
  • mice transmit increased susceptibility to DSS-induced colitis to co-housed wild-type mice
  (MGI Ref ID J:173245)

hematopoietic system phenotype

• impaired neutrophil chemotaxis
  • less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae
  (MGI Ref ID J:125285)

immune system phenotype

• increased susceptibility to bacterial infection
  • bacterial counts in the lung are 20-fold higher one day after infection with Haemophilus influenzae
  (MGI Ref ID J:125285)
  • there is less inflammation present in the lungs 6- and 24- hours after infection with histological scores significantly reduced compared to wild-type mice
  (MGI Ref ID J:125285)
  • Normal - mice are able to clear infection from the lungs 10 days after infection, which is similar to wild-type mice
  (MGI Ref ID J:125285)

• increased susceptibility to induced colitis
  • mice exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis compared with similarly treated wild-type mice
  (MGI Ref ID J:173245)
  • mice transmit increased susceptibility to DSS-induced colitis to co-housed wild-type mice
  (MGI Ref ID J:173245)

• impaired neutrophil chemotaxis
  • less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae
  (MGI Ref ID J:125285)