Mouse Genome Informatics
hm1
    Ifngtm1Ts/Ifngtm1Ts
B6.129S7-Ifngtm1Ts
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• sudden death occurs 5 to 7 weeks after infection with Leishmania major (J:18801)
• die earlier after inoculation with Toxoplasma gondii (strain ME49) compared to wild-type controls (J:110826)
• higher mortality is seen following infection with JHMV compared to wild-type controls
• Background Sensitivity: in mice on a C57BL/6 background compared to mice on a BALB/c background

tumorigenesis
• Background Sensitivity: 50% of mice on a congenic C57BL/5 background develop disseminated lymphomas compared to 0% of mice on a congenic BALB/c background
• most lymphomas are diffuse large cell lymphomas
• in a few mice
• Background Sensitivity: in mice on a C57BL/6 background compared to mice on a BALB/c background

immune system
• increase in the number of CD8+ cells in the white matter tracts of JHMV infected mice compared to similarly infected wild-type controls at 7 and 14 days post infection
• immature B cells fail to be excluded from the lymph nodes
• after infection with Leishmania major
• after infection with Leishmania major (J:18801)
• 5-fold increase in the serum levels of JHMV specific IgG1 at 14 days post infection compared to infected wild-type controls (J:112048)
• after infection with Leishmania major
• after infection with Leishmania major
• significant increase in the numbers of immature B cells in the lymph nodes
• after infection with Leishmania major the number of lymphocytes producing IL4 increases unlike in control mice where the number of lymphocytes producing IFNG increases (J:18801)
• following infection with T. gondii (irradiate RH strain) splenocytes show enhanced Th2 cytokine production compared to similar cultures from wild-type mice (J:110826)
• cervical lymph node cells from JHMV infected mice (7 days post infection) secrete more IL10 in response to JHMV antigen compared to cells from similarly infected wild-type mice
• cervical lymph node cells from JHMV infected mice secrete more IL2 in response to JHMV antigen compared to cells from similarly infected wild-type mice
• cervical lymph node cells from JHMV infected mice (7 days post infection) secrete more IL5 in response to JHMV antigen compared to cells from similarly infected wild-type mice
• after infection with Leishmania major mice display minimal Th1 type responses and increased Th2 type responses (J:18801)
• after infection with Leishmania major levels of IgG1 and IgE are increased while levels of IgG2a and IgG3 remain low (J:18801)
• following infection with T. gondii (irradiate RH strain) splenocytes show enhanced Th2 cytokine production compared to similar cultures from wild-type mice (J:110826)
• develop progressive infection characterized by large lesions at the site of inoculation and sudden death 5 to 7 weeks after infection with Leishmania major
• numbers of parasites present in the footpads are substantially increased compared to wild-type and heterozygous controls
• sudden death occurs 5 to 7 weeks after infection with Leishmania major (J:18801)
• die earlier after inoculation with Toxoplasma gondii (strain ME49) compared to wild-type controls (J:110826)
• following infection with the JHM strain of mouse hepatitis virus (JHMV) mice display a slower clinical recovery and higher viral titers in the central nervous system compared to wild-type controls
• however, no differences are found in JHMV specific cytotoxic T lymphocyte activity
• at 14 days post infection with JHMV a 10 fold increase in the number of viral antigen positive cells is detected in the brain with most of the infected cells being oligodendrocytes
• higher mortality is seen following infection with JHMV compared to wild-type controls
• after immunosuppressive treatment (anti-CD4 and anti-CD8 mAbs) allografts (BALB/c, H2-Ab1bm12 continue to display myocardial rejection at week 12 but do not display graft arterial disease, in contrast wild-type mice at week 12 display low levels of rejection but develop coronary arteriopathy

hematopoietic system
• increase in the number of CD8+ cells in the white matter tracts of JHMV infected mice compared to similarly infected wild-type controls at 7 and 14 days post infection
• immature B cells fail to be excluded from the lymph nodes
• after infection with Leishmania major
• after infection with Leishmania major (J:18801)
• 5-fold increase in the serum levels of JHMV specific IgG1 at 14 days post infection compared to infected wild-type controls (J:112048)
• after infection with Leishmania major
• after infection with Leishmania major


Mouse Genome Informatics
hm2
    Ifngtm1Ts/Ifngtm1Ts
B6.129S7-Ifngtm1Ts/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• increase in mortality following a single dose of N-methyl-N-nitrosourea (MNU) compared to similarly treated wild-type controls
• die by 6 - 10 weeks after infection with the avirulent BCG strain of Mycobacterium bovis
• most mice die by 9 days after infection with 1x106 Cryptosporidium parvum oocysts

immune system
N
• do not exhibit defects on either IgE isotype switch or IgE production (J:114783)
• 5 days after muscle injury fewer macrophages are present at the injury site compared to similarly treated wild-type mice
• 5 weeks after Helicobacter pylori infection, mice have a significantly decreased gastritis inflammation score compared to infected wild-type mice
• following infection with BCG
• in the blood, bone marrow and spleen following infection with BCG
• unlike in wild-type mice, treatment with LPS and DGalN fails to decrease NK T cell numbers
• following infection with BCG
• following infection with BCG, the normal follicular structure of the red and white pulp is lost and the red pulp is replaced with extramedullary hematopoietic tissue
• develop splenomegaly after infection with BCG
• following infection with BCG, the normal follicular structure of the red and white pulp is lost and the lymphocytic populations of the white pulp are replaced with sheets of leukocytes
• spleens become paler as BCG infection proceeds
• increase in circulating levels of CSF3 after infection with BCG especially in moribund mice
• following infection with BCG
• in C. parvum infected mice
• increase in IL12 and decrease in IL10 secretion following LPS stimulation
• enhancement in the ability of dendritic cells to transmigrate across a membrane in response to RANTES in vitro
• enhancement in LPS induced dendritic cell migration to the spleen
• enhancement in hapten induced Langerhan cell migration to the draining lymph nodes
• dendritic cells show a greater ability to stimulate T cell proliferation in vitro
• in OVA fed mice only a modest decrease in the delayed type hypersensitivity response to injected OVA is seen in contrast this reaction is strongly decreased in similarly treated wild-type controls
• display a more severe delayed type hypersensitivity reaction in response to sheep IgG
• the magnitude of the OVA specific antibody response to subcutaneous OVA challenge is reduced
• however, following oral OVA exposure OVA antibody levels in response to subcutaneous OVA challenge are essentially unchanged unlike in wild-type controls where oral exposure reduces antibody levels
• IgG responses are restricted to IgG1 and IgG2b
• splenocytes fail to produce IFN-gamma in response to H. pylori antigen stimulation
• splenocytes from Helicobacter pylori infected mice produce 4-fold less IL-10 when cultured in the presence of H. pylori antigen (J:120556)
• by bone marrow dendritic cells following LPS stimulation (J:134949)
• by bone marrow dendritic cells following LPS stimulation
• splenocytes from Helicobacter pylori infected mice produce significantly more IL-4 than splenocytes from wild-type controls when cultured in the presence of H. pylori antigen
• oral exposure to antigen (OVA) fails to reduce the responsiveness of mice to subsequent subcutaneous exposure to the same antigen
• increased susceptibility to induced accelerated antiglomerular basement membrane nephritis as determined by increased albuminuria and more severe pathological changes
• following infection with BCG mice display an increased bacterial load throughout the infect in contrast to wild-type mice where bacterial numbers peak at 17 days post infection and decline thereafter
• following infection with BCG mice develop numerous granulomatous lesions in the liver and necrosis of both the liver and spleen
• die by 6 - 10 weeks after infection with the avirulent BCG strain of Mycobacterium bovis
• Background Sensitivity: mice on a C57BL/6 background lose weight and develop soft gelatinous stools over the course of a C. parvum infection while mice on a BALB/c background do not
• Background Sensitivity: in C. parvum infected mice on a C57BL/6 background, but not on a BALB/c background, the gastrointestinal tract is heavily colonized with parasites, the small intestines are distended and filled with gelatinous fluid, mesenteric lymph nodes are enlarged and in about 50% of mice gallbladders are enlarged
• most mice die by 9 days after infection with 1x106 Cryptosporidium parvum oocysts
• decrease in survival times of heart transplants from CBA mice after a 30 day course of anti-CD4 and anti-CD8 mAb
• only 10% of heart grafts survive more than 100 days compared to 36% of grafts in wild-type mice

behavior/neurological
• Background Sensitivity: increase in the number of defecations following a sound stimulus suggesting an enhancement of fear related responses in mice on a C57BL/6 background but not in mice on a BALB/c background
• prolonged freeze time and longer time to return to normal open field activity patterns following a startle stimulus relative to wild-type controls
• make fewer entries and spend less time in the open arms of an elevated maze relative to wild-type controls
• Background Sensitivity: increase in the number of defecations in a novel environment compared to wild-type controls in mice on a C57BL/6 background but not in mice on a BALB/c background
• the number of rearings is decreased in a novel environment
• initial locomotor activity is decreased; however, overall distance traveled is not different from controls
• in a novel environment

cellular
• enhancement in the ability of dendritic cells to transmigrate across a membrane in response to RANTES in vitro
• enhancement in LPS induced dendritic cell migration to the spleen
• 5 days after muscle injury fewer macrophages are present at the injury site compared to similarly treated wild-type mice
• unlike in wild-type mice, treatment with LPS and DGalN or TNF-alpha and interferon-gamma fails to increase the production of reactive oxygen species in hepatocytes

renal/urinary system
• 1 day after induction of accelerated antiglomerular basement membrane nephritis no increase in total urinary nitrate or nitrate levels is detected unlike in similarly treated wild-type controls
• increase in albuminuria on days 2, 3,and 4 following induction of accelerated antiglomerular basement membrane nephritis
• increased susceptibility to induced accelerated antiglomerular basement membrane nephritis as determined by increased albuminuria and more severe pathological changes

homeostasis/metabolism
• increase in circulating levels of CSF3 after infection with BCG especially in moribund mice
• following infection with BCG
• unlike in wild-type mice, treatment with LPS and DGalN fails to increase nitric oxide levels
• 1 day after induction of accelerated antiglomerular basement membrane nephritis no increase in total urinary nitrate or nitrate levels is detected unlike in similarly treated wild-type controls
• increase in albuminuria on days 2, 3,and 4 following induction of accelerated antiglomerular basement membrane nephritis
• increase in mortality following a single dose of N-methyl-N-nitrosourea (MNU) compared to similarly treated wild-type controls
• decrease in the number and area of regenerating muscle fibers 5 and 10 days after muscle injury
• fibrotic lesions are sometimes seen after injury
• 5 days after muscle injury fewer macrophages are present at the injury site compared to similarly treated wild-type mice
• following a 48 h exposure to hyperoxia (98-99% oxygen) neutrophil migration into the lung air space and the increase in pulmonary alveolar permeability are decreased indicating a decrease susceptibility to the early phase of hyperoxia induced lung injury
• however, after 84 h of exposure to hyperoxia these measures are not different from similarly exposed to wild-type controls
• fibrotic lesions are sometimes seen after injury

muscle
• fibrotic lesions are sometimes seen after injury
• decrease in the number and area of regenerating fibers 5 and 10 days after injury
• fibrotic lesions are sometimes seen after injury
• however, prior to injury no difference in muscle fiber morphology are detected

digestive/alimentary system
• 5 weeks after Helicobacter pylori infection, mice have a significantly decreased gastritis inflammation score compared to infected wild-type mice

hematopoietic system
• 5 days after muscle injury fewer macrophages are present at the injury site compared to similarly treated wild-type mice
• following infection with BCG
• in the blood, bone marrow and spleen following infection with BCG
• unlike in wild-type mice, treatment with LPS and DGalN fails to decrease NK T cell numbers
• following infection with BCG
• following infection with BCG
• following infection with BCG, the normal follicular structure of the red and white pulp is lost and the red pulp is replaced with extramedullary hematopoietic tissue
• develop splenomegaly after infection with BCG
• following infection with BCG, the normal follicular structure of the red and white pulp is lost and the lymphocytic populations of the white pulp are replaced with sheets of leukocytes
• spleens become paler as BCG infection proceeds
• IgG responses are restricted to IgG1 and IgG2b


Mouse Genome Informatics
hm3
    Ifngtm1Ts/Ifngtm1Ts
C.129S7(B6)-Ifngtm1Ts/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die by 6 - 10 weeks after infection with the avirulent BCG strain of Mycobacterium bovis

immune system
• 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 (J:56503)
• after day 10 of gestation increased numbers of uNK cells are found in the metrial gland compared to wild-type controls (J:56503)
• following infection with BCG
• in the blood, bone marrow and spleen following infection with BCG
• following infection with BCG
• following infection with BCG, the normal follicular structure of the red and white pulp is lost and the red pulp is replaced with extramedullary hematopoietic tissue
• develop splenomegaly after infection with BCG
• following infection with BCG, the normal follicular structure of the red and white pulp is lost and the lymphocytic populations of the white pulp are replaced with sheets of leukocytes
• spleens become paler as BCG infection proceeds
• increase in circulating levels of CSF3 after infection with BCG especially in moribund mice
• following infection with BCG
• decrease in the cytotoxicity of NK cells from mice primed with rIL12
• decrease in the number of apoptotic uNK cells in the metrial gland afte day 10 of gestation (J:56503)
• uNK cells at implantation sites fail to become heavily granulated and have poorly developed golgi apparati (J:56503)
• C26 cells induce slightly reduced CTL activity compared to the response in similarly treat wild-type mice
• exposure to rIL12 fails to prime macrophages against subsequent LPS exposure
• lymphocytes form C25/Il12 cell primed mice produce about 3 fold higher levels of CSF2
• in C26/Il12 tumors CD4+ T cells are more numerous relative to CD8+ T cells, in tumors in wild-type mice CD8+ T cells are more numerous
• following infection with BCG mice display an increased bacterial load throughout the infect in contrast to wild-type mice where bacterial numbers peak at 17 days post infection and decline thereafter
• following infection with BCG mice develop numerous granulomatous lesions in the liver and necrosis of both the liver and spleen
• die by 6 - 10 weeks after infection with the avirulent BCG strain of Mycobacterium bovis
• Background Sensitivity: unlike mice on a C57BL/6 background, mice on a BALB/c background do not lose weight, show any change in stool consistency, or display heavy parasitic loads in the gastrointestinal tract over the course of a C. parvum infection

behavior/neurological
• prolonged freeze time following a startle stimulus relative to wild-type controls
• Background Sensitivity: no increase in the number of defecations following a sound stimulus is seen in mice on a BALB/c background unlike mice on a C57BL/6 background
• the number of rearings is decreased in a novel environment
• Background Sensitivity: unlike mice on a C57BL/6 background, no increase in the number of defecations in a novel environment or following a sound stimulus is seen in mice on a BALB/c background, compared to wild-type controls
• in a novel environment

tumorigenesis
• when injected with 5 x 105 C26/Il12 cells only a few mice are able to reject the tumor, in contrast 80 - 100% of wild-type mice reject the tumor
• in C26/Il12 derived tumors, tumor vessels are more numerous and thinner compared to vessels in tumors in wild-type mice
• tumor onset is accelerated in 40% of mice injected with 5 x 104 C26 carcinoma cells transduced with Il12 genes (C26/Il12) compared to similarly treated wild-type mice
• however, no difference is detected when parental C26 cells are used

reproductive system
• after gestational day 10 the intercellular composition of the decidua changes suggesting accumulations of fluid and extracellular matrix, areas of necrosis are present and a lack of decidual cellularity is apparent (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 (J:56503)
• after day 10 of gestation increased numbers of uNK cells are found in the metrial gland compared to wild-type controls (J:56503)
• decrease in the number of apoptotic uNK cells in the metrial gland afte day 10 of gestation (J:56503)
• uNK cells at implantation sites fail to become heavily granulated and have poorly developed golgi apparati (J:56503)
• decrease in litter size and increase in the number of resorbed embryos in the first litter
• no difference in litter size or number of resorbed embryos is detected in subsequent pregnancies
• phenotype is independent of the genotype of the embryos

homeostasis/metabolism
• increase in circulating levels of CSF3 after infection with BCG especially in moribund mice
• following infection with BCG

embryogenesis
• after gestational day 10 the intercellular composition of the decidua changes suggesting accumulations of fluid and extracellular matrix, areas of necrosis are present and a lack of decidual cellularity is apparent (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 (J:56503)
• after day 10 of gestation increased numbers of uNK cells are found in the metrial gland compared to wild-type controls (J:56503)

hematopoietic system
• 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 (J:56503)
• after day 10 of gestation increased numbers of uNK cells are found in the metrial gland compared to wild-type controls (J:56503)
• following infection with BCG
• in the blood, bone marrow and spleen following infection with BCG
• following infection with BCG
• following infection with BCG
• following infection with BCG, the normal follicular structure of the red and white pulp is lost and the red pulp is replaced with extramedullary hematopoietic tissue
• develop splenomegaly after infection with BCG
• following infection with BCG, the normal follicular structure of the red and white pulp is lost and the lymphocytic populations of the white pulp are replaced with sheets of leukocytes
• spleens become paler as BCG infection proceeds
• decrease in the cytotoxicity of NK cells from mice primed with rIL12
• decrease in the number of apoptotic uNK cells in the metrial gland afte day 10 of gestation (J:56503)
• uNK cells at implantation sites fail to become heavily granulated and have poorly developed golgi apparati (J:56503)
• C26 cells induce slightly reduced CTL activity compared to the response in similarly treat wild-type mice
• exposure to rIL12 fails to prime macrophages against subsequent LPS exposure


Mouse Genome Informatics
hm4
    Ifngtm1Ts/Ifngtm1Ts
C.129S7-Ifngtm1Ts
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• the LD50 for Listeria monocytogenes infection is 10 CFU compared to greater than 104 CFU for wild-type and heterozygous controls
• however the LD50 for a mutant strain of L. monocytogenes (DP-L1942) is similar in homozygous mice and controls
• following vaccination mice are able to develop resistance to L. monocytogenes infection
• die within 9 days of inoculation with T. gondii (strain ME49) unlike controls which survive more than 30 days
• highly susceptible to the normally avirulent T. gondii isolate, ts4

immune system
• the magnitude of the OVA specific antibody is reduced
• following oral OVA exposure OVA antibody levels are essentially unchanged unlike in wild-type controls where oral exposure reduces antibody levels
• IgG responses are restricted to IgG1 and IgG2b
• following infection with T. gondii (irradiate RH strain) splenocytes show enhanced Th2 cytokine production compared to similar cultures from wild-type mice
• following infection with T. gondii (irradiate RH strain) splenocytes produce more IL-5 compared to similar cultures from wild-type mice
• oral exposure to antigen (OVA) fails to reduce the responsiveness of mice to subsequent exposure to the same antigen
• incidence rate (17 of 24 compared to 1 of 16 in controls) and severity are increased compared to contols immunization results in about a 30% mortality rate
• immunized mice display meningeal and perivascular inflammatory infiltrates in the spinal cord and brain similar to those seen in susceptible strains like SJL/J
• following infection with T. gondii (irradiate RH strain) splenocytes show enhanced Th2 cytokine production compared to similar cultures from wild-type mice
• the LD50 for Listeria monocytogenes infection is 10 CFU compared to greater than 104 CFU for wild-type and heterozygous controls
• however the LD50 for a mutant strain of L. monocytogenes (DP-L1942) is similar in homozygous mice and controls
• following vaccination mice are able to develop resistance to L. monocytogenes infection
• dramatic increase in the number of infected cells expansion of the tissues infected following inoculation with Toxoplasma gondii (strain ME49)
• 5 days after inoculation with T. gondii (strain ME49) peritoneal exudates contain a more pronounced increase in the numbers of granulocytes, eosinophils, and mast cells compared to similarly infected wild-type controls
• IL-2 production in response to infection is similar to controls
• die within 9 days of inoculation with T. gondii (strain ME49) unlike controls which survive more than 30 days
• highly susceptible to the normally avirulent T. gondii isolate, ts4

tumorigenesis
N
• Background Sensitivity: unlike mice on a congenic C57BL/6 background, mice on a BALB/c background do not develop disseminated lymphomas (J:77491)
• in a few mice, with a very late onset
• all are well differentiated papillary adenocarcinomas
• Background Sensitivity: in mice on a BALB/c background compared to mice on a C57BL/6 background

hematopoietic system
• IgG responses are restricted to IgG1 and IgG2b


Mouse Genome Informatics
hm5
    Ifngtm1Ts/Ifngtm1Ts
involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mean survival time following infecting with virulent Mycobacterium tuberculosis is 15 days compared to over 60 days for wild-type controls
• treatment with exogenous IFNG improves survival
• more than 70% of mice infected on the cornea with herpes simplex virus type 1 (HSV-1) at a dose of 105 TCID50 (50% tissue culture infective dose) infectious particles die

immune system
• in mice with acute or chronic HSV-1 infection the ratio of IgG2a to IgG1 is dramatically reduced compared to BALB/c wild-type mice
• following infection with type A influenza
• activated splenic and liver NK cells are less efficient in their killing of 4T1 or Renca tumor target cells
• T cells from mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide show more IL-17a expressing cells and greater IL-17a production after MOG restimulation than controls; IL-4 is not detectable in these cells
• the magnitude of the delayed type hypersensitive response in mice after HSV-1 infection is reduced compared to BALB/c wild-type controls
• following culturing of IL-17 producing T cells in vitro, IL-17 production is twice as high as in similarly treated wild-type cells
• the magnitude of the delayed type hypersensitive response in mice after HSV-1 infection is reduced compared to BALB/c wild-type controls (J:29170)
• display an increased IgG1 antibody response to type A influenza infection (J:110721)
• 14 days after infection with virulent Mycobacterium tuberculosis serum levels of reactive nitrogen intermediates are very low, unlike in wild-type controls (J:110856)
• at 14 days after infection with virulent Mycobacterium tuberculosis, 10- 100 fold more viable bacteria are found in the organs compared to organs of wild-type controls
• at 14 days after infection with virulent Mycobacterium tuberculosis, about 90% of the granulomas in the liver and 20% of the granulomas in the spleen are necrotic
• treatment with exogenous IFNG decreases the bacterial load
• mean survival time following infecting with virulent Mycobacterium tuberculosis is 15 days compared to over 60 days for wild-type controls
• treatment with exogenous IFNG improves survival
• at 5 - 8 days post infection mice develop more severe conjunctivitis, periocular skin lesions, corneal opacity, and anterior chamber exudate following infection with HSV-1 relative to wld-type BALB/c controls infected with a higher dose of virus
• infectious virus is detected up to 10 days post infection with HSV-1 in mutants compared to up to 4 or days post infection in wild-type BAL/c mice or littermate controls, respectively
• more than 70% of mice infected on the cornea with herpes simplex virus type 1 (HSV-1) at a dose of 105 TCID50 (50% tissue culture infective dose) infectious particles die

vision/eye
• corneal injection of a plasmid encoding short hairpin RNA targeting the C terminus of the secreted form of Flt1 (pshRNA-sflt1) induces corneal vascularization within 3 days of injection in wild-type and mutant mice

homeostasis/metabolism
• T cells from mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide show more IL-17a expressing cells and greater IL-17a production after MOG restimulation than controls; IL-4 is not detectable in these cells

cardiovascular system
• corneal injection of a plasmid encoding short hairpin RNA targeting the C terminus of the secreted form of Flt1 (pshRNA-sflt1) induces corneal vascularization within 3 days of injection in wild-type and mutant mice

hematopoietic system
• in mice with acute or chronic HSV-1 infection the ratio of IgG2a to IgG1 is dramatically reduced compared to BALB/c wild-type mice
• following infection with type A influenza
• activated splenic and liver NK cells are less efficient in their killing of 4T1 or Renca tumor target cells


Mouse Genome Informatics
hm6
    Ifngtm1Ts/Ifngtm1Ts
involves: 129S7/SvEvBrd * A/WySn * C57BL/10SnSg * Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• relative to wild-type controls
• however, mercury treatment does not result in an increase in IgG1 levels
• decrease in the induction of IgG in response to low levels of antigen ((4-hydroxy-3 nitrophenyl)acetyl)
• following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice
• resistant to mercury induced autoimmune response

homeostasis/metabolism
• resistant to mercury induced autoimmune response

hematopoietic system
• relative to wild-type controls
• however, mercury treatment does not result in an increase in IgG1 levels
• decrease in the induction of IgG in response to low levels of antigen ((4-hydroxy-3 nitrophenyl)acetyl)
• following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice


Mouse Genome Informatics
hm7
    Ifngtm1Ts/Ifngtm1Ts
involves: 129S7/SvEvBrd * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• no difference in survival, tissue damage or spread of infection following infection with the opportunistic fungal pathogen Candida albicans is detected relative to wild-type controls (J:39881)
• ovalbumin challenge fails to significantly potentiate ovalbumin specific IgE levels, unlike in wild-type controls
• the eosinophilic response in ovalbumin challenged mice is reduced compared to wild-type controls
• mice are able to clear infectious Murine gammaherpesvirus 68 (MHV-68) from their lungs but with a slight delay relative wild-type mice
• no differences are detected in the frequency of latently infected cells, the generation of cytotoxic T cells, the infection induced cytokine profile, or the recruitment or proliferation of cells into inflammatory sites

respiratory system
• ovalbumin challenge fails to induce airway hyperresponsiveness unlike in wild-type mice
• in saline challenged mice relative to wild-type controls

hematopoietic system
• ovalbumin challenge fails to significantly potentiate ovalbumin specific IgE levels, unlike in wild-type controls


Mouse Genome Informatics
hm8
    Ifngtm1Ts/Ifngtm1Ts
involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• mice are able to clear infections of Pneumocystis carinii, similar to controls (J:119206)
• splenocytes from BCG infected mice exhibit increased proliferation in response to Con A
• significantly lower resting splenic NK cell activity (J:66802)
• recruitment of NK cells to the liver by recombinant murine IL12 is impaired (J:115033)
• however, the recruitment of T cells by IL12 is not impaired (J:115033)
• macrophages from BCG infected mice fail to produce nitric oxide in response to LPS challenge
• macrophages from BCG infected mice exhibit reduced production of superoxide anion in response to PMA challenge
• macrophages from BCG infected mice exhibit reduced class II expression
• exposure to UVA and UVB fails to significantly reduce the UVB induced suppression of the type IV hypersensitivity reaction
• however, the type IV hypersensitivity reaction in the absence of UV exposure is similar to controls
• increased mortality following a sublethal dose of Mycobacterium bovis (BCG )
• mice infected with Plasmodium berghei ANKA are protected from development of experimental cerebral malaria and survive longer than wild-type mice
• however, IFNG-competent alpha+CD4+ T cells promote experimental cerebral malaria
• mice infected with Plasmodium berghei ANKA are protected from development of experimental cerebral malaria and survive longer than wild-type mice
• reduced surival of cardiac grafts relative to controls

tumorigenesis
• following treatment with alphaGalCer, mice fail to exhibit a reduction in the number of B16F10 tumors metastasizing to the lungs unlike similarly treated wild-type mice
• tumor-bearing mice treated with Th-17-polarized cells from Tg(Tcra,Tcrb)9Rest cells show increased tumor rejection compared to controls

craniofacial
• modest increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks

skeleton
• modest increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks

hematopoietic system
• splenocytes from BCG infected mice exhibit increased proliferation in response to Con A
• significantly lower resting splenic NK cell activity (J:66802)
• recruitment of NK cells to the liver by recombinant murine IL12 is impaired (J:115033)
• however, the recruitment of T cells by IL12 is not impaired (J:115033)
• macrophages from BCG infected mice fail to produce nitric oxide in response to LPS challenge
• macrophages from BCG infected mice exhibit reduced production of superoxide anion in response to PMA challenge
• macrophages from BCG infected mice exhibit reduced class II expression

integument
• following exposure to UVA and UVB mice fail to develop significant erythema unlike wild-type controls
• however, the increase in skin fold thickness in response to UVB or UVA and UVB exposure is not significantly different from controls

cellular
• splenocytes from BCG infected mice exhibit increased proliferation in response to Con A

mortality/aging
• mice infected with Plasmodium berghei ANKA are protected from development of experimental cerebral malaria and survive longer than wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Malaria, Susceptibility to 611162 J:189794


Mouse Genome Informatics
hm9
    Ifngtm1Ts/Ifngtm1Ts
involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• after infection with a normally sublethal dose of the virulent Erdam strain of Mycobacterium tuberculosis mice become severely ill and need to be euthanized

immune system
• following infection with a sublethal dose of the virulent Erdam strain of Mycobacterium tuberculosis mice develop widespread infection with high numbers of bacteria in multiple tissues and obvious bacteremia
• by 4 weeks after aerosol infection with the virulent Erdam strain of Mycobacterium tuberculosis mice display multifocal necrotic areas contain high numbers of bacteria in the spleen, liver, lungs and kidneys
• after infection with a normally sublethal dose of the virulent Erdam strain of Mycobacterium tuberculosis mice become severely ill and need to be euthanized


Mouse Genome Informatics
hm10
    Ifngtm1Ts/Ifngtm1Ts
involves: 129S7/SvEvBrd * DBA/1 * MRL/Mp
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 3 months of age relative to wild-type controls
• at 3 and 7-8 months of age relative to wild-type controls
• at 3 and 7-8 months of age relative to wild-type controls
• at 3 months of age relative to wild-type controls
• at 3 months of age relative to wild-type controls
• older mice appear to be protected from end organ disease relative to wild-type controls
• levels of anti-snRNP antibodies are decreased at 3 but not at 7-8 months of age relative to wild-type controls
• at 3 and 7-8 months of age relative to wild-type controls
• at 3 months of age relative to wild-type controls
• at 7 -8 months of age levels of anti-dsDNA antibodies are similar to wild-type controls but these antibodies fail to bind dsDNA containing kinetoplast of Crithidia luciliae substrates suggesting the antibodies are of low affinity

hematopoietic system
• at 3 months of age relative to wild-type controls
• at 3 and 7-8 months of age relative to wild-type controls
• at 3 and 7-8 months of age relative to wild-type controls
• at 3 months of age relative to wild-type controls
• at 3 months of age relative to wild-type controls


Mouse Genome Informatics
hm11
    Ifngtm1Ts/Ifngtm1Ts
involves: 129S7/SvEvBrd * NOD
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• Background Sensitivity: at generation N4 no difference is seen in the time course of diabetes development in females unlike in mice at generation N7 (J:33427)


Mouse Genome Informatics
hm12
    Ifngtm1Ts/Ifngtm1Ts
NOD.129S7(B6)-Ifngtm1Ts Prkdcscid
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• when diabetic NOD splenocytes are transferred into mutant NOD.scid mice only 23% of recipients become diabetic (determined by monitoring urine glucose level) 7 weeks after transfer, but 100% of wild-type NOD.Scid mice are diabetic within 5 weeks

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:72818


Mouse Genome Informatics
hm13
    Ifngtm1Ts/Ifngtm1Ts
NOD.129S7(B6)-Ifngtm1Ts/DvsJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• CD8+ T cells injected into Ifng-deficient NOD mice are less able to cause diabetes, due to impaired homing ability and impaired diapedesis
• when diabetic NOD splenocytes are transferred into mutant NOD mice, only 33% develop diabetes over the course of the observation period

endocrine/exocrine glands
• islet cells from Ifng-deficient NOD mice are less susceptible to insulin-specific CD8+ cell-induced toxicity

hematopoietic system
• CD8+ T cells injected into Ifng-deficient NOD mice are less able to cause diabetes, due to impaired homing ability and impaired diapedesis

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:72818


Mouse Genome Informatics
hm14
    Ifngtm1Ts/Ifngtm1Ts
NOD.129S7-Ifngtm1Ts
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• Background Sensitivity: delay in the development of diabetes in females at generation N7 but not a generation N4
• however, the ultimate penetrance of the diabetes phenotype does not differ from wild-type controls and no gross differences in pancreatic inflammation are detected
• null animals challenged with CVB4 at 8 weeks of age show a retarded rate of diabetes (2 consecutive blood glucose measures >240 mg/dl) development compared to saline-treated controls; over the 25-week follow up period, about 30% of CVB4-exposed nulls develop disease versus around 90% of aline-treated controls


Mouse Genome Informatics
cn15
    Ifngtm1Ts/Ifngtm1Ts
Tgfbr2tm1.2Hlm/Tgfbr2tm1.2Hlm
Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
Tg(Cd4-cre)1Cwi/0

involves: 129 * C57BL/6 * DBA/2 * NOD * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• improved survival (J:196160)

immune system
N
• do not develop diabetes (J:196160)


Mouse Genome Informatics
cn16
    Foxo1tm1Flv/Foxo1tm1Flv
Ifngtm1Ts/Ifngtm1Ts
Foxp3tm4(YFP/cre)Ayr/Foxp3+

involves: 129S1/Sv * 129S6/SvEvTac * 129S7/SvEvBrd * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• the lethal inflammatory phenotype is partially rescued (J:189962)

immune system
N
• regulatory T cells are able to suppress development of colitis in Rag1 null mice receiving na[?]ve T cells (J:189962)
• elevated numbers in the spleen and peripheral lymph nodes are partially rescued compared to in Foxo1tm1Flv/Foxo1tm1Flv Foxp3/Foxp3+ mice
• elevated numbers in the spleen and peripheral lymph nodes are partially rescued compared to in Foxo1tm1Flv/Foxo1tm1Flv Foxp3/Foxp3+ mice

hematopoietic system
• elevated numbers in the spleen and peripheral lymph nodes are partially rescued compared to in Foxo1tm1Flv/Foxo1tm1Flv Foxp3/Foxp3+ mice
• elevated numbers in the spleen and peripheral lymph nodes are partially rescued compared to in Foxo1tm1Flv/Foxo1tm1Flv Foxp3/Foxp3+ mice


Mouse Genome Informatics
cx17
    Apoetm1Unc/Apoetm1Unc
Ifngtm1Ts/Ifngtm1Ts

B6.129-Apoetm1Unc Ifngtm1Ts
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• about 50% of mice infused with angiotensin-II die within 2 to 10 days due to rupture of the abdominal aorta compared to 0 deaths of mutant mice wild-type for Ifng

cardiovascular system
• about 50% of mice infused with 1000 ng/kg*min angiotensin-II die within 2 to 10 days due to rupture of the abdominal aorta compared to 0 deaths of mutant mice wild-type for Ifng
• increase in the incidence of abdominal aorta aneurysyms in in mice infused with 500 ng/kg*min angiotensin-II compared to mutant mice wild-type for Ifng
• increase in the suprarenal aortic diameter in mice infused with 500 ng/kg*min angiotensin-II compared to mutant mice wild-type for Ifng

growth/size
• compared to mutant mice wild-type for Ifng


Mouse Genome Informatics
cx18
    Csf2tm1Mlg/Csf2tm1Mlg
Ifngtm1Ts/Ifngtm1Ts
Il3tm1Glli/Il3tm1Glli

B6.129S-Csf2tm1Mlg Il3tm1Glli Ifngtm1TsIfngtm1Ts
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• significantly reduced fasting blood sugar, to levels similar to controls (J:145518)
• improved glucose tolerance (J:145518)

tumorigenesis


Mouse Genome Informatics
cx19
    Ifngtm1Ts/Ifngtm1Ts
Ldlrtm1Her/Ldlrtm1Her

B6.129S7-Ldlrtm1Her Ifngtm1Ts
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• after 8 or 20 weeks on a cholesterol diet aortic lesion size is reduced compared to mice homozygous for Ldlrtm1Her alone

hematopoietic system
• increase in the proportion of T cells in the blood relative to controls homozygous for Ldlrtm1Her alone

immune system
• increase in the proportion of T cells in the blood relative to controls homozygous for Ldlrtm1Her alone


Mouse Genome Informatics
cx20
    Ifngtm1Ts/Ifngtm1Ts
Tgfb1tm1Doe/Tgfb1tm1Doe

C.129-Ifngtm1Ts Tgfb1tm1Doe
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice survive average of 32.9 days (range 23-66 days)

growth/size
• mice are smaller than littermate controls

liver/biliary system
N
• outwardly, livers show no visible abnormalities (J:69346)
• on necropsy, modest inflammatory expansion around portal tracts is observed in some animals

immune system
• on necropsy, modest inflammatory expansion around portal tracts is observed in some animals

homeostasis/metabolism
• in 4/5 mice >21 days of age, ALT plasma levels are elevated


Mouse Genome Informatics
cx21
    Ifngtm1Ts/Ifngtm1Ts
Prf1tm1Sdz/Prf1tm1Sdz

C.Cg-Prf1tm1Sdz Ifngtm1Ts
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

tumorigenesis
• some lymphomas have an unusual histiocytic appearance with a pale eosinophilic cytoplasm
• incidence is increased and onset is earlier compared to mice homozygous for Prf1tm1Sdz alone
• incidence is increased and onset is earlier compared to mice homozygous for Prf1tm1Sdz alone


Mouse Genome Informatics
cx22
    Ifngtm1Ts/Ifngtm1Ts
Tnfrsf1atm1Blt/Tnfrsf1atm1Blt
Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm

involves: 129P2/OlaHsd * 129S2/SvPas * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• despite the absence of germinal centers the white pulp has distinct T and B cell areas
• grossly unidentifiable and histologically hypoplastic
• thin and lack primary and secondary cortical follicles
• develop severe inflammation 4 weeks after infection with Pneumocystis carinii
• 4 weeks after infection with Pneumocystis carinii lungs demonstrate severe infection indicating mice are unable to clear the infection
• 4 weeks after infection with Pneumocystis carinii pulmonary lavages contain about 10 fold higher numbers of leukocytes compared to similarly infected control mice

hematopoietic system
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• despite the absence of germinal centers the white pulp has distinct T and B cell areas

respiratory system
• develop severe inflammation 4 weeks after infection with Pneumocystis carinii


Mouse Genome Informatics
cx23
    Ifngtm1Ts/Ifngtm1Ts
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• development and severity of IBD are similar to Tnftm2Gkl/+, wild-type Ifng controls

digestive/alimentary system
• development and severity of IBD are similar to Tnftm2Gkl/+, wild-type Ifng controls


Mouse Genome Informatics
cx24
    Ifngtm1Ts/Ifngtm1Ts
Socs1tm1Wehi/Socs1tm1Wehi

involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• unlike mice homozygous for Socs1tm1Wehi alone, double homozygous mice survive past weaning and are overtly healthy (J:57474)
• lethality observed in Socs1tm1Wehi homozygotes is rescued (J:70408)

reproductive system
• from day 16 of pregnancy, mice exhibit a higher density of lobuloalveolar units compared with wild-type mice (J:70408)
• however, proliferation of mammary epithelium is normal (J:70408)

endocrine/exocrine glands
• from day 16 of pregnancy, mice exhibit a higher density of lobuloalveolar units compared with wild-type mice (J:70408)
• however, proliferation of mammary epithelium is normal (J:70408)
• from day 16 of pregnancy, mice exhibit a higher density of lobuloalveolar units compared with wild-type mice (J:70408)
• however, lobuloalveolar density returns to normal by day 5 of lactation (J:70408)
• 8 of 12 mice have enlarged medulla
• however, unlike mice homozygous for Socs1tm1Wehi alone, the cortex is normal
• at day 18 of pregnancy, mammary glands produce more milk than in wild-type mice (J:70408)

cardiovascular system
• 2 of 12 mice show lymphoid cuffing of the lung vessels

hematopoietic system
N
• unlike mice homozygous for Socs1tm1Wehi alone, no hematological abnormalities are detected at 3 weeks of age (J:57474)
• 8 of 12 mice have enlarged medulla
• however, unlike mice homozygous for Socs1tm1Wehi alone, the cortex is normal

immune system
• 8 of 12 mice have enlarged medulla
• however, unlike mice homozygous for Socs1tm1Wehi alone, the cortex is normal

respiratory system
• 2 of 12 mice show lymphoid cuffing of the lung vessels

integument
• from day 16 of pregnancy, mice exhibit a higher density of lobuloalveolar units compared with wild-type mice (J:70408)
• however, proliferation of mammary epithelium is normal (J:70408)
• from day 16 of pregnancy, mice exhibit a higher density of lobuloalveolar units compared with wild-type mice (J:70408)
• however, lobuloalveolar density returns to normal by day 5 of lactation (J:70408)
• at day 18 of pregnancy, mammary glands produce more milk than in wild-type mice (J:70408)


Mouse Genome Informatics
cx25
    Ifngtm1Ts/Ifng+
Socs1tm1Wehi/Socs1tm1Wehi

involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 8 of 12 mice died between 2 and 12 weeks of age, the remaining 4 survived
• 8 of 12 mice died between 2 and 12 weeks of age, the remaining 4 survived


Mouse Genome Informatics
cx26
    Csf2tm1Dran/Csf2tm1Dran
Ifngtm1Ts/Ifngtm1Ts
Il3tm1Glli/Il3tm1Glli

involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• about 40% of homozygotes died of pneumonia in the first few weeks of life
• surviving mice became moribund with time
• most died or had to be euthanized before 14 months of age

immune system
• mild eosinophilia in mice surviving beyond the first few weeks of life
• serum levels increased but not significantly
• non significant increases in serum IgG2b levels
• significantly higher serum IgG1 levels
• acute and chronic inflammatory reactions found in many organs and tissues

tumorigenesis
• Lymphoproliferative disease in a high proportion of mice
• develops into B cell lymphomas
• solid tumors are benign to metastasizing carcinomas
• particularly prevalent (J:83086)

hematopoietic system
• mild eosinophilia in mice surviving beyond the first few weeks of life
• serum levels increased but not significantly
• significantly higher serum IgG1 levels
• non significant increases in serum IgG2b levels

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Systemic Lupus Erythematosus; SLE 152700 J:83086


Mouse Genome Informatics
cx27
    Ifngtm1Ts/Ifngtm1Ts
Socs1tm1Jni/Socs1tm1Jni

involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• following culturing of IL-17 producing T cells in vitro, IL-17 production is twice as high as in similarly treated wild-type cells


Mouse Genome Informatics
cx28
    Ifngtm1Ts/Ifngtm1Ts
Nlrp1aNeut1/Nlrp1aNeut1

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• normal blood neutrophils and survival (J:191055)
• develop encephalitis

nervous system
• develop encephalitis


Mouse Genome Informatics
cx29
    Faslpr/Faslpr
Ifngtm1Ts/Ifngtm1Ts

involves: 129S7/SvEvBrd * DBA/1 * MRL/Mp
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• decrease in the number of CD4-CD8-B220+ alpha beta T cells compared to mice homozygous for Faslpr and wild-type for Ifng
• lympadenopathy (based on spleen weight and cellularity) is reduced compared to mice homozygous for Faslpr and wild-type for Ifng
• at 7-8 months of age a modest increase in spleen size and cellularity is seen relative to wild-type controls
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Ifng
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Ifng
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Ifng
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Ifng
• lympadenopathy (based on lymph node weight and cellularity) is reduced compared to mice homozygous for Faslpr and wild-type for Ifng
• in young animals lymph node size is similar to wild-type controls
• at 7-8 months of age a modest increase in lymph node size and cellularity is seen relative to wild-type controls
• while mice develop the typical autoimmune lesions, end organ disease is decreased compared to mice homozygous for Faslpr and wild-type for Ifng
• lower titers of anti-snRNP and anti-rheumatoid factors antibodies relative to mice homozygous for Faslpr and wild-type for Ifng at 3 and 7-8 months of age
• at 3 and 7-8 months of age

homeostasis/metabolism
• levels are lower compared to mice homozygous for Faslpr and wild-type for Ifng

hematopoietic system
• decrease in the number of CD4-CD8-B220+ alpha beta T cells compared to mice homozygous for Faslpr and wild-type for Ifng
• lympadenopathy (based on spleen weight and cellularity) is reduced compared to mice homozygous for Faslpr and wild-type for Ifng
• at 7-8 months of age a modest increase in spleen size and cellularity is seen relative to wild-type controls
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Ifng
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Ifng
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Ifng
• at 3 and 7-8 months of age relative to mice homozygous for Faslpr and wild-type for Ifng


Mouse Genome Informatics
cx30
    Faslpr/Faslpr
Ifngtm1Ts/Ifngtm1Ts

MRL.Cg-Ifngtm1Ts Faslpr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• at 4 months, kidney-infiltrating macrophages are not present; deposits of glomerular immune complexes (ICs) are not observed (J:123834)
• in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages, IC deposition and glomerular proliferation are similar to control mice not receiving transfers (J:123834)
• in mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months, kidney interstitium remains free of macrophages, T cells, or other lymphocytes (signs of kidney interstitial inflammation) at 2 months post-transfer (J:123834)
• in mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months, anti-DNA autoantibody production is minimal compared to Ifng-wild-type, Faslpr homozygotes; glomerular autoantibody deposits are not observed (J:123834)
• macrophage accumulation is reduced compared to Faslpr homozygotes
• in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages, migration of macrophages to peritubular and periglomerular areas of kidneys is detected, whereas without transfer, macrophage recruitment to these areas is significantly reduced relative to Faslpr homozygotes
• mice display perivascular infiltrate composed mainly of CD4+ cells
• mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months develop heavy perivascular infiltrates of mainly CD4+ T cells but show no signs of glomerular nephritis, similar to nontransferred controls
• severe multifocal pyogranulomatous nephritis is observed in kidneys of mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months of age, with extensive perivascular and periglomerular accumulation of polymorphonuclear leukocytes and mononuclear cells
• mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months develop diffuse severe acidophilic pneumonia, characterized by intraalveolar accumulation of strongly eosinophilic macrophages with heavy CD3+ cell infiltration; some animals present with peribronchial T cell infiltration

renal/urinary system
• mice display perivascular infiltrate composed mainly of CD4+ cells
• mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months develop heavy perivascular infiltrates of mainly CD4+ T cells but show no signs of glomerular nephritis, similar to nontransferred controls
• severe multifocal pyogranulomatous nephritis is observed in kidneys of mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months of age, with extensive perivascular and periglomerular accumulation of polymorphonuclear leukocytes and mononuclear cells
• in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages, glomerular nephritis is not observed, but severe multifocal pyogranulomatous nephritis in kidneys is observed

respiratory system
• mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months develop diffuse severe acidophilic pneumonia, characterized by intraalveolar accumulation of strongly eosinophilic macrophages with heavy CD3+ cell infiltration; some animals present with peribronchial T cell infiltration

cellular
• macrophage accumulation is reduced compared to Faslpr homozygotes
• in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages, migration of macrophages to peritubular and periglomerular areas of kidneys is detected, whereas without transfer, macrophage recruitment to these areas is significantly reduced relative to Faslpr homozygotes

hematopoietic system
• macrophage accumulation is reduced compared to Faslpr homozygotes
• in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages, migration of macrophages to peritubular and periglomerular areas of kidneys is detected, whereas without transfer, macrophage recruitment to these areas is significantly reduced relative to Faslpr homozygotes


Mouse Genome Informatics
cx31
    Faslpr/Faslpr
Ifngtm1Ts/Ifng+

MRL.Cg-Ifngtm1Ts Faslpr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice become moribund and are sacrificed at 4 months mutants posttransfer of Ifng wild-type F4/80+ macrophages at 2 months while all controls remain alive

immune system
• macrophage accumulation is reduced compared to Faslpr homozygotes
• mice develop glomerular autoantibody deposits, but do not develop glomerulonephritis
• mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months develop diffuse proliferative glomerulonephritis by 6 months

renal/urinary system
• glomeruli are hypercellular in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months
• glomerular damage is more severe in mice receiving cell transfer than in control mice not receiving transfers
• thickening of capillary walls in glomeruli is observed in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months
• mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months develop diffuse proliferative glomerulonephritis by 6 months
• mesangial cells are increased in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

homeostasis/metabolism
• BUN levels are elevated at time of death in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

cardiovascular system
• thickening of capillary walls in glomeruli is observed in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

cellular
• macrophage accumulation is reduced compared to Faslpr homozygotes

hematopoietic system
• macrophage accumulation is reduced compared to Faslpr homozygotes