Phenotypes associated with this allele

• Allele Symbol: Ifng^tm1Ts
• Allele Name: targeted mutation 1, Timothy Stewart
• Allele ID: MGI:1857184
• Summary: 33 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ifng^tm1Ts/Ifng^tm1Ts	B6.129S7-Ifng^tm1Ts	MGI:4365971
hm2	Ifng^tm1Ts/Ifng^tm1Ts	B6.129S7-Ifng^tm1Ts/J	MGI:3696100
hm3	Ifng^tm1Ts/Ifng^tm1Ts	C.129S7(B6)-Ifng^tm1Ts/J	MGI:4839056
hm4	Ifng^tm1Ts/Ifng^tm1Ts	C.129S7-Ifng^tm1Ts	MGI:4838443
hm5	Ifng^tm1Ts/Ifng^tm1Ts	involves: 129S7/SvEvBrd	MGI:3693883
hm6	Ifng^tm1Ts/Ifng^tm1Ts	involves: 129S7/SvEvBrd * A/WySn * C57BL/10SnSg * Swiss	MGI:4843967
hm7	Ifng^tm1Ts/Ifng^tm1Ts	involves: 129S7/SvEvBrd * BALB/c	MGI:4838445
hm8	Ifng^tm1Ts/Ifng^tm1Ts	involves: 129S7/SvEvBrd * C57BL/6	MGI:3587743
hm9	Ifng^tm1Ts/Ifng^tm1Ts	involves: 129S7/SvEvBrd * C57BL/6J	MGI:4838441
hm10	Ifng^tm1Ts/Ifng^tm1Ts	involves: 129S7/SvEvBrd * DBA/1 * MRL/Mp	MGI:4839050
hm11	Ifng^tm1Ts/Ifng^tm1Ts	involves: 129S7/SvEvBrd * NOD	MGI:4838444
hm12	Ifng^tm1Ts/Ifng^tm1Ts	NOD.129S7(B6)-Ifng^tm1Ts/DvsJ	MGI:3623449
hm13	Ifng^tm1Ts/Ifng^tm1Ts	NOD.129S7-Ifng^tm1Ts	MGI:3622412
hm14	Ifng^tm1Ts/Ifng^tm1Ts	NOD.Cg-Ifng^tm1Ts Prkdc^scid	MGI:3623448
cn15	Ifng^tm1Ts/Ifng^tm1Ts Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0 Tg(Cd4-cre)1Cwi/0	involves: 129 * C57BL/6 * DBA/2 * NOD * SJL	MGI:5514242
cn16	Foxo1^tm1Flv/Foxo1^tm1Flv Ifng^tm1Ts/Ifng^tm1Ts Foxp3^tm4(YFP/icre)Ayr/Foxp3^+	involves: 129S1/Sv * 129S6/SvEvTac * 129S7/SvEvBrd * 129X1/SvJ	MGI:5448156
cx17	Apoe^tm1Unc/Apoe^tm1Unc Ifng^tm1Ts/Ifng^tm1Ts	B6.129-Apoe^tm1Unc Ifng^tm1Ts	MGI:4938323
cx18	Ifng^tm1Ts/Ifng^tm1Ts Ldlr^tm1Her/Ldlr^tm1Her	B6.129S7-Ldlr^tm1Her Ifng^tm1Ts	MGI:4867042
cx19	Csf2^tm1Mlg/Csf2^tm1Mlg Ifng^tm1Ts/Ifng^tm1Ts Il3^tm1Glli/Il3^tm1Glli	B6.129S-Csf2^tm1Mlg Il3^tm1Glli Ifng^tm1TsIfng^tm1Ts	MGI:5431918
cx20	Ifng^tm1Ts/Ifng^tm1Ts Tgfb1^tm1Doe/Tgfb1^tm1Doe	C.129-Ifng^tm1Ts Tgfb1^tm1Doe	MGI:3721950
cx21	Ifng^tm1Ts/Ifng^tm1Ts Prf1^tm1Sdz/Prf1^tm1Sdz	C.Cg-Prf1^tm1Sdz Ifng^tm1Ts	MGI:4867045
cx22	Ifng^tm1Ts/Ifng^tm1Ts Pld4^tm1.2Nemz/Pld4^tm1.2Nemz	involves: 129 * 129S7/SvEvBrd * C57BL/6J * FVB/N	MGI:6452102
cx23	Ifng^tm1Ts/Ifng^tm1Ts Tnfrsf1a^tm1Blt/Tnfrsf1a^tm1Blt Tnfrsf1b^tm1Mwm/Tnfrsf1b^tm1Mwm	involves: 129P2/OlaHsd * 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:4843969
cx24	Ifng^tm1Ts/Ifng^tm1Ts Socs1^tm1Wehi/Socs1^tm1Wehi	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6	MGI:4430638
cx25	Ifng^tm1Ts/Ifng^+ Socs1^tm1Wehi/Socs1^tm1Wehi	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6	MGI:4850158
cx26	Csf2^tm1Dran/Csf2^tm1Dran Ifng^tm1Ts/Ifng^tm1Ts Il3^tm1Glli/Il3^tm1Glli	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:3586344
cx27	Ifng^tm1Ts/Ifng^tm1Ts Socs1^tm1Jni/Socs1^tm1Jni	involves: 129S7/SvEvBrd	MGI:3783715
cx28	Ifng^tm1Ts/Ifng^tm1Ts Nlrp1a^Neut1/Nlrp1a^Neut1	involves: 129S7/SvEvBrd * C57BL/6	MGI:5474288
cx29	Ifng^tm1Ts/Ifng^tm1Ts Tg(SFTPC-Il18)AThos/0	involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6N * DBA/2	MGI:5688500
cx30	Fas^lpr/Fas^lpr Ifng^tm1Ts/Ifng^tm1Ts	involves: 129S7/SvEvBrd * DBA/1 * MRL/Mp	MGI:4839049
cx31	Ifng^tm1Ts/Ifng^tm1Ts Tnf^tm2Gkl/Tnf^+	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6J	MGI:3629594
cx32	Fas^lpr/Fas^lpr Ifng^tm1Ts/Ifng^tm1Ts	MRL.Cg-Ifng^tm1Ts Fas^lpr	MGI:3801418
cx33	Fas^lpr/Fas^lpr Ifng^tm1Ts/Ifng^+	MRL.Cg-Ifng^tm1Ts Fas^lpr	MGI:3801419

Genotype
MGI:4365971

hm1

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: B6.129S7-Ifng^tm1Ts

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

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:77491 )

• in a few mice

mortality/aging

increased susceptibility to parasitic infection induced morbidity/mortality ( J:18801 , J:110826 )

• 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)

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:112048 )

• higher mortality is seen following infection with JHMV compared to wild-type controls

premature death ( J:77491 )

• Background Sensitivity: in mice on a C57BL/6 background compared to mice on a BALB/c background

neoplasm

increased lymphoma incidence ( J:77491 )

• 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

increased T cell derived lymphoma incidence ( J:77491 )

• in a few mice

increased sarcoma incidence ( J:77491 )

• in a few mice

decreased tumor latency ( J:77491 )

• Background Sensitivity: in mice on a C57BL/6 background compared to mice on a BALB/c background

immune system

increased CD8-positive, alpha-beta T cell number ( J:112048 )

• 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

abnormal B cell physiology ( J:112084 )

• immature B cells fail to be excluded from the lymph nodes

abnormal immunoglobulin level ( J:18801 )

increased IgE level ( J:18801 )

• after infection with Leishmania major

increased IgG1 level ( J:18801 , J:112048 )

• 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)

decreased IgG2a level ( J:18801 )

• after infection with Leishmania major

decreased IgG3 level ( J:18801 )

• after infection with Leishmania major

abnormal lymph node cell ratio ( J:112084 )

• significant increase in the numbers of immature B cells in the lymph nodes

abnormal cytokine secretion ( J:18801 , J:110826 )

• 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)

increased interleukin-10 secretion ( J:112048 )

• 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

increased interleukin-2 secretion ( J:112048 )

• 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

increased interleukin-5 secretion ( J:112048 )

• 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

abnormal response to infection ( J:18801 , J:110826 )

• 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)

increased susceptibility to parasitic infection ( J:18801 )

• 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

increased susceptibility to parasitic infection induced morbidity/mortality ( J:18801 , J:110826 )

• 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)

increased susceptibility to Coronaviridae infection ( J:112048 )

• 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

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:112048 )

• higher mortality is seen following infection with JHMV compared to wild-type controls

abnormal response to transplant ( J:42090 )

• after immunosuppressive treatment (anti-CD4 and anti-CD8 mAbs) allografts (BALB/c, H2-Ab1^bm12 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

increased CD8-positive, alpha-beta T cell number ( J:112048 )

• 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

abnormal B cell physiology ( J:112084 )

• immature B cells fail to be excluded from the lymph nodes

abnormal immunoglobulin level ( J:18801 )

increased IgE level ( J:18801 )

• after infection with Leishmania major

increased IgG1 level ( J:18801 , J:112048 )

• 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)

decreased IgG2a level ( J:18801 )

• after infection with Leishmania major

decreased IgG3 level ( J:18801 )

• after infection with Leishmania major

Genotype
MGI:3696100

hm2

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: B6.129S7-Ifng^tm1Ts/J

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:91927 )

• increase in mortality following a single dose of N-methyl-N-nitrosourea (MNU) compared to similarly treated wild-type controls

increased susceptibility to bacterial infection induced morbidity/mortality ( J:47459 )

• die by 6 - 10 weeks after infection with the avirulent BCG strain of Mycobacterium bovis

increased susceptibility to parasitic infection induced morbidity/mortality ( J:50832 )

• most mice die by 9 days after infection with 1x10⁶ Cryptosporidium parvum oocysts

immune system

immune system phenotype ( J:114783 )

N • do not exhibit defects on either IgE isotype switch or IgE production

abnormal macrophage chemotaxis ( J:136628 )

• 5 days after muscle injury fewer macrophages are present at the injury site compared to similarly treated wild-type mice

stomach inflammation ( J:120556 )

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

increased leukocyte cell number ( J:47459 )

• following infection with BCG

increased granulocyte number ( J:47459 )

• in the blood, bone marrow and spleen following infection with BCG

increased NK T cell number ( J:122801 )

• unlike in wild-type mice, treatment with LPS and DGalN fails to decrease NK T cell numbers

increased monocyte cell number ( J:47459 )

• following infection with BCG

abnormal spleen morphology ( J:47459 )

enlarged spleen ( J:47459 )

• develop splenomegaly after infection with BCG

abnormal spleen red pulp morphology ( J:47459 )

• 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

abnormal spleen white pulp morphology ( J:47459 )

• 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

pale spleen ( J:47459 )

• spleens become paler as BCG infection proceeds

abnormal circulating cytokine level ( J:47459 )

• increase in circulating levels of CSF3 after infection with BCG especially in moribund mice

increased circulating interleukin-6 level ( J:47459 )

• following infection with BCG

enlarged mesenteric lymph nodes ( J:50832 )

• in C. parvum infected mice

abnormal dendritic cell physiology ( J:134949 )

• increase in IL12 and decrease in IL10 secretion following LPS stimulation

abnormal dendritic cell chemotaxis ( J:134949 )

• 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

abnormal Langerhans cell physiology ( J:134949 )

• enhancement in hapten induced Langerhan cell migration to the draining lymph nodes

abnormal dendritic cell antigen presentation ( J:134949 )

• dendritic cells show a greater ability to stimulate T cell proliferation in vitro

abnormal type IV hypersensitivity reaction ( J:45665 )

• 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

increased susceptibility to type IV hypersensitivity reaction ( J:118730 )

• display a more severe delayed type hypersensitivity reaction in response to sheep IgG

abnormal humoral immune response ( J:45665 )

• 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

abnormal immunoglobulin level ( J:45665 )

• IgG responses are restricted to IgG1 and IgG2b

abnormal cytokine secretion ( J:120556 )

decreased interferon-gamma secretion ( J:120556 )

• splenocytes fail to produce IFN-gamma in response to H. pylori antigen stimulation

decreased interleukin-10 secretion ( J:120556 , J:134949 )

• 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)

increased interleukin-12 secretion ( J:134949 )

• by bone marrow dendritic cells following LPS stimulation

increased interleukin-4 secretion ( J:120556 )

• 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

abnormal immune tolerance ( J:45665 )

• oral exposure to antigen (OVA) fails to reduce the responsiveness of mice to subsequent subcutaneous exposure to the same antigen

glomerulonephritis ( J:118730 )

• increased susceptibility to induced accelerated antiglomerular basement membrane nephritis as determined by increased albuminuria and more severe pathological changes

increased susceptibility to bacterial infection ( J:47459 )

• 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

increased susceptibility to bacterial infection induced morbidity/mortality ( J:47459 )

• die by 6 - 10 weeks after infection with the avirulent BCG strain of Mycobacterium bovis

increased susceptibility to parasitic infection ( J:50832 )

• 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

increased susceptibility to parasitic infection induced morbidity/mortality ( J:50832 )

• most mice die by 9 days after infection with 1x10⁶ Cryptosporidium parvum oocysts

decreased length of allograft survival ( J:44346 )

• 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

abnormal response to new environment ( J:54250 )

• 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

increased fear-related response ( J:54250 )

• 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

decreased vertical activity ( J:54250 )

• in a novel environment

cellular

abnormal dendritic cell chemotaxis ( J:134949 )

• 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

abnormal macrophage chemotaxis ( J:136628 )

• 5 days after muscle injury fewer macrophages are present at the injury site compared to similarly treated wild-type mice

abnormal redox activity ( J:122801 )

• 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

abnormal urine homeostasis ( J:118730 )

• 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

albuminuria ( J:118730 )

• increase in albuminuria on days 2, 3,and 4 following induction of accelerated antiglomerular basement membrane nephritis

glomerulonephritis ( J:118730 )

• increased susceptibility to induced accelerated antiglomerular basement membrane nephritis as determined by increased albuminuria and more severe pathological changes

homeostasis/metabolism

abnormal circulating cytokine level ( J:47459 )

• increase in circulating levels of CSF3 after infection with BCG especially in moribund mice

increased circulating interleukin-6 level ( J:47459 )

• following infection with BCG

abnormal nitric oxide homeostasis ( J:122801 )

• unlike in wild-type mice, treatment with LPS and DGalN fails to increase nitric oxide levels

abnormal urine homeostasis ( J:118730 )

• 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

albuminuria ( J:118730 )

• increase in albuminuria on days 2, 3,and 4 following induction of accelerated antiglomerular basement membrane nephritis

increased susceptibility to xenobiotic induced morbidity/mortality ( J:91927 )

• increase in mortality following a single dose of N-methyl-N-nitrosourea (MNU) compared to similarly treated wild-type controls

abnormal response to injury ( J:136628 )

• 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

decreased susceptibility to injury ( J:108148 )

• 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

muscle

skeletal muscle fibrosis ( J:136628 )

• fibrotic lesions are sometimes seen after injury

impaired skeletal muscle regeneration ( J:136628 )

• 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

stomach inflammation ( J:120556 )

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

hematopoietic system

abnormal dendritic cell chemotaxis ( J:134949 )

• 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

abnormal macrophage chemotaxis ( J:136628 )

• 5 days after muscle injury fewer macrophages are present at the injury site compared to similarly treated wild-type mice

extramedullary hematopoiesis ( J:47459 )

• following infection with BCG

increased leukocyte cell number ( J:47459 )

• following infection with BCG

increased granulocyte number ( J:47459 )

• in the blood, bone marrow and spleen following infection with BCG

increased NK T cell number ( J:122801 )

• unlike in wild-type mice, treatment with LPS and DGalN fails to decrease NK T cell numbers

increased monocyte cell number ( J:47459 )

• following infection with BCG

abnormal spleen morphology ( J:47459 )

enlarged spleen ( J:47459 )

• develop splenomegaly after infection with BCG

abnormal spleen red pulp morphology ( J:47459 )

• 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

abnormal spleen white pulp morphology ( J:47459 )

• 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

pale spleen ( J:47459 )

• spleens become paler as BCG infection proceeds

abnormal immunoglobulin level ( J:45665 )

• IgG responses are restricted to IgG1 and IgG2b

growth/size/body

enlarged spleen ( J:47459 )

• develop splenomegaly after infection with BCG

Genotype
MGI:4839056

hm3

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: C.129S7(B6)-Ifng^tm1Ts/J

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:47459 )

• die by 6 - 10 weeks after infection with the avirulent BCG strain of Mycobacterium bovis

immune system

abnormal uterine NK cell morphology ( J:56503 )

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

increased uterine NK cell number ( J:56503 )

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

increased leukocyte cell number ( J:47459 )

• following infection with BCG

increased granulocyte number ( J:47459 )

• in the blood, bone marrow and spleen following infection with BCG

increased monocyte cell number ( J:47459 )

• following infection with BCG

abnormal spleen morphology ( J:115144 )

enlarged spleen ( J:47459 )

• develop splenomegaly after infection with BCG

abnormal spleen red pulp morphology ( J:47459 )

• 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

abnormal spleen white pulp morphology ( J:47459 )

• 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

pale spleen ( J:47459 )

• spleens become paler as BCG infection proceeds

abnormal circulating cytokine level ( J:47459 )

• increase in circulating levels of CSF3 after infection with BCG especially in moribund mice

increased circulating interleukin-6 level ( J:47459 )

• following infection with BCG

abnormal adaptive immunity ( J:115144 )

abnormal NK cell physiology ( J:115144 )

• decrease in the cytotoxicity of NK cells from mice primed with rIL12

abnormal uterine NK cell physiology ( J:56503 )

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

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

abnormal cytotoxic T cell physiology ( J:115144 )

• C26 cells induce slightly reduced CTL activity compared to the response in similarly treat wild-type mice

abnormal macrophage physiology ( J:115144 )

• exposure to rIL12 fails to prime macrophages against subsequent LPS exposure

abnormal cytokine secretion ( J:115144 )

• lymphocytes form C25/Il12 cell primed mice produce about 3 fold higher levels of CSF2

abnormal inflammatory response ( J:115144 )

• 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

increased susceptibility to bacterial infection ( J:47459 )

• 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

increased susceptibility to bacterial infection induced morbidity/mortality ( J:47459 )

• die by 6 - 10 weeks after infection with the avirulent BCG strain of Mycobacterium bovis

decreased susceptibility to parasitic infection ( J:50832 )

• 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

abnormal response to new environment ( J:54250 )

• 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

increased fear-related response ( J:54250 )

• 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

decreased vertical activity ( J:54250 )

• in a novel environment

neoplasm

abnormal tumor pathology ( J:115144 )

• 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

decreased tumor latency ( J:115144 )

• 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

abnormal maternal decidual layer morphology ( J:56503 )

♀ • 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

abnormal uterine NK cell morphology ( J:56503 )

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

increased uterine NK cell number ( J:56503 )

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

abnormal uterine NK cell physiology ( J:56503 )

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

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

decreased litter size ( 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

abnormal circulating cytokine level ( J:47459 )

• increase in circulating levels of CSF3 after infection with BCG especially in moribund mice

increased circulating interleukin-6 level ( J:47459 )

• following infection with BCG

embryo

abnormal maternal decidual layer morphology ( J:56503 )

♀ • 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

abnormal uterine NK cell morphology ( J:56503 )

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

increased uterine NK cell number ( J:56503 )

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

hematopoietic system

abnormal uterine NK cell morphology ( J:56503 )

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

increased uterine NK cell number ( J:56503 )

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

extramedullary hematopoiesis ( J:47459 )

• following infection with BCG

increased leukocyte cell number ( J:47459 )

• following infection with BCG

increased granulocyte number ( J:47459 )

• in the blood, bone marrow and spleen following infection with BCG

increased monocyte cell number ( J:47459 )

• following infection with BCG

abnormal spleen morphology ( J:115144 )

enlarged spleen ( J:47459 )

• develop splenomegaly after infection with BCG

abnormal spleen red pulp morphology ( J:47459 )

• 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

abnormal spleen white pulp morphology ( J:47459 )

• 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

pale spleen ( J:47459 )

• spleens become paler as BCG infection proceeds

abnormal NK cell physiology ( J:115144 )

• decrease in the cytotoxicity of NK cells from mice primed with rIL12

abnormal uterine NK cell physiology ( J:56503 )

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

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

abnormal cytotoxic T cell physiology ( J:115144 )

• C26 cells induce slightly reduced CTL activity compared to the response in similarly treat wild-type mice

abnormal macrophage physiology ( J:115144 )

• exposure to rIL12 fails to prime macrophages against subsequent LPS exposure

endocrine/exocrine glands

abnormal uterine NK cell morphology ( J:56503 )

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

increased uterine NK cell number ( J:56503 )

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

growth/size/body

enlarged spleen ( J:47459 )

• develop splenomegaly after infection with BCG

Genotype
MGI:4838443

hm4

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: C.129S7-Ifng^tm1Ts

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:83180 )

• 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

increased susceptibility to parasitic infection induced morbidity/mortality ( J:110826 )

• 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

abnormal humoral immune response ( J:45665 )

• 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

abnormal immunoglobulin level ( J:45665 )

• IgG responses are restricted to IgG1 and IgG2b

abnormal cytokine secretion ( J:110826 )

• following infection with T. gondii (irradiate RH strain) splenocytes show enhanced Th2 cytokine production compared to similar cultures from wild-type mice

increased interleukin-5 secretion ( J:110826 )

• following infection with T. gondii (irradiate RH strain) splenocytes produce more IL-5 compared to similar cultures from wild-type mice

abnormal immune tolerance ( J:45665 )

• oral exposure to antigen (OVA) fails to reduce the responsiveness of mice to subsequent exposure to the same antigen

increased susceptibility to experimental autoimmune encephalomyelitis ( J:34161 )

• 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

abnormal response to infection ( J:110826 )

• following infection with T. gondii (irradiate RH strain) splenocytes show enhanced Th2 cytokine production compared to similar cultures from wild-type mice

increased susceptibility to bacterial infection induced morbidity/mortality ( J:83180 )

• 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

increased susceptibility to parasitic infection ( J:110826 )

• 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

increased susceptibility to parasitic infection induced morbidity/mortality ( J:110826 )

• 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

neoplasm

neoplasm ( J:77491 )

N • Background Sensitivity: unlike mice on a congenic C57BL/6 background, mice on a BALB/c background do not develop disseminated lymphomas

increased lung adenocarcinoma incidence ( J:77491 )

• in a few mice, with a very late onset

• all are well differentiated papillary adenocarcinomas

increased tumor latency ( J:77491 )

• Background Sensitivity: in mice on a BALB/c background compared to mice on a C57BL/6 background

hematopoietic system

abnormal immunoglobulin level ( J:45665 )

• IgG responses are restricted to IgG1 and IgG2b

respiratory system

increased lung adenocarcinoma incidence ( J:77491 )

• in a few mice, with a very late onset

• all are well differentiated papillary adenocarcinomas

Genotype
MGI:3693883

hm5

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:110856 )

• 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

increased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:29170 )

• 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

abnormal immunoglobulin level ( J:29170 )

• 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

increased IgG1 level ( J:110721 )

• following infection with type A influenza

impaired natural killer cell mediated cytotoxicity ( J:73948 )

• activated splenic and liver NK cells are less efficient in their killing of 4T1 or Renca tumor target cells

abnormal cytokine level ( J:112600 )

• 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

decreased susceptibility to type IV hypersensitivity reaction ( J:29170 )

• the magnitude of the delayed type hypersensitive response in mice after HSV-1 infection is reduced compared to BALB/c wild-type controls

increased interleukin-17 secretion ( J:132905 )

• following culturing of IL-17 producing T cells in vitro, IL-17 production is twice as high as in similarly treated wild-type cells

abnormal response to infection ( J:29170 , J:110721 )

• 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)

increased susceptibility to bacterial infection ( 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

increased susceptibility to bacterial infection induced morbidity/mortality ( J:110856 )

• 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

increased susceptibility to Herpesvirales infection ( J:29170 )

• 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

increased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:29170 )

• 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 vascularization ( J:114973 )

• 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

abnormal cytokine level ( J:112600 )

• 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 vascularization ( J:114973 )

• 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

abnormal immunoglobulin level ( J:29170 )

• 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

increased IgG1 level ( J:110721 )

• following infection with type A influenza

impaired natural killer cell mediated cytotoxicity ( J:73948 )

• activated splenic and liver NK cells are less efficient in their killing of 4T1 or Renca tumor target cells

Genotype
MGI:4843967

hm6

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: involves: 129S7/SvEvBrd * A/WySn * C57BL/10SnSg * Swiss

immune system

increased IgG1 level ( J:119207 )

• relative to wild-type controls

• however, mercury treatment does not result in an increase in IgG1 levels

decreased IgG level ( J:119207 )

• decrease in the induction of IgG in response to low levels of antigen ((4-hydroxy-3 nitrophenyl)acetyl)

decreased IgG2a level ( J:119207 )

• following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice

decreased susceptibility to autoimmune disorder ( J:119207 )

• resistant to mercury induced autoimmune response

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:119207 )

• resistant to mercury induced autoimmune response

hematopoietic system

increased IgG1 level ( J:119207 )

• relative to wild-type controls

• however, mercury treatment does not result in an increase in IgG1 levels

decreased IgG level ( J:119207 )

• decrease in the induction of IgG in response to low levels of antigen ((4-hydroxy-3 nitrophenyl)acetyl)

decreased IgG2a level ( J:119207 )

• following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice

Genotype
MGI:4838445

hm7

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: involves: 129S7/SvEvBrd * BALB/c

immune system

immune system phenotype ( J:39881 )

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

decreased IgE level ( J:114213 )

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

decreased inflammatory response ( J:114213 )

• the eosinophilic response in ovalbumin challenged mice is reduced compared to wild-type controls

abnormal susceptibility to infection ( J:39478 )

• 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

decreased airway responsiveness ( J:114213 )

• ovalbumin challenge fails to induce airway hyperresponsiveness unlike in wild-type mice

increased airway responsiveness ( J:114213 )

• in saline challenged mice relative to wild-type controls

hematopoietic system

decreased IgE level ( J:114213 )

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

Genotype
MGI:3587743

hm8

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

immune system

immune system phenotype ( J:119206 )

N • mice are able to clear infections of Pneumocystis carinii, similar to controls

increased splenocyte proliferation ( J:66802 )

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

abnormal NK cell physiology ( J:66802 , J:115033 )

• 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)

abnormal macrophage physiology ( J:66802 )

• 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

abnormal MHC II cell surface expression on macrophages ( J:66802 )

• macrophages from BCG infected mice exhibit reduced class II expression

abnormal type IV hypersensitivity reaction ( J:55740 )

• 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 susceptibility to bacterial infection ( J:66802 )

• increased mortality following a sublethal dose of Mycobacterium bovis (BCG )

decreased susceptibility to parasitic infection ( J:189794 )

• 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

decreased susceptibility to parasitic infection induced morbidity/mortality ( J:189794 )

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

decreased length of allograft survival ( J:44346 )

• reduced surival of cardiac grafts relative to controls

growth/size/body

alveolar process atrophy ( J:147935 )

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

neoplasm

increased metastatic potential ( J:152785 )

• 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

decreased tumor incidence ( J:138466 )

• tumor-bearing mice treated with Th-17-polarized cells from Tg(Tcra,Tcrb)9Rest cells show increased tumor rejection compared to controls

craniofacial

alveolar process atrophy ( J:147935 )

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

skeleton

alveolar process atrophy ( J:147935 )

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

hematopoietic system

increased splenocyte proliferation ( J:66802 )

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

abnormal NK cell physiology ( J:66802 , J:115033 )

• 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)

abnormal macrophage physiology ( J:66802 )

• 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

abnormal MHC II cell surface expression on macrophages ( J:66802 )

• macrophages from BCG infected mice exhibit reduced class II expression

integument

abnormal skin physiology ( J:55740 )

• 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

increased splenocyte proliferation ( J:66802 )

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

mortality/aging

decreased susceptibility to parasitic infection induced morbidity/mortality ( J:189794 )

• 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		DO ID	OMIM ID(s)	Ref(s)
malaria		DOID:12365		J:189794

Genotype
MGI:4838441

hm9

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:15723 )

• 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

increased susceptibility to bacterial infection ( J:15723 )

• 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

increased susceptibility to bacterial infection induced morbidity/mortality ( J:15723 )

• after infection with a normally sublethal dose of the virulent Erdam strain of Mycobacterium tuberculosis mice become severely ill and need to be euthanized

Genotype
MGI:4839050

hm10

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: involves: 129S7/SvEvBrd * DBA/1 * MRL/Mp

immune system

decreased immunoglobulin level ( J:39600 )

decreased IgA level ( J:39600 )

• at 3 months of age relative to wild-type controls

decreased IgG2a level ( J:39600 )

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

decreased IgG2b level ( J:39600 )

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

decreased IgG3 level ( J:39600 )

• at 3 months of age relative to wild-type controls

decreased IgM level ( J:39600 )

• at 3 months of age relative to wild-type controls

decreased susceptibility to autoimmune disorder ( J:39600 )

• older mice appear to be protected from end organ disease relative to wild-type controls

decreased autoantibody level ( J:39600 )

• levels of anti-snRNP antibodies are decreased at 3 but not at 7-8 months of age relative to wild-type controls

decreased anti-nuclear antigen antibody level ( J:39600 )

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

decreased anti-double stranded DNA antibody level ( J:39600 )

• 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

decreased immunoglobulin level ( J:39600 )

decreased IgA level ( J:39600 )

• at 3 months of age relative to wild-type controls

decreased IgG2a level ( J:39600 )

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

decreased IgG2b level ( J:39600 )

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

decreased IgG3 level ( J:39600 )

• at 3 months of age relative to wild-type controls

decreased IgM level ( J:39600 )

• at 3 months of age relative to wild-type controls

Genotype
MGI:4838444

hm11

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: involves: 129S7/SvEvBrd * NOD

immune system

immune system phenotype ( J:33427 )

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

Genotype
MGI:3623449

hm12

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: NOD.129S7(B6)-Ifng^tm1Ts/DvsJ

cellular

abnormal diapedesis ( J:72818 )

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

immune system

abnormal diapedesis ( J:72818 )

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

abnormal cytotoxic T cell physiology ( J:72818 )

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

decreased susceptibility to autoimmune diabetes ( J:72818 )

• when diabetic NOD splenocytes are transferred into mutant NOD mice, only 33% develop diabetes over the course of the observation period

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:72818 )

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

hematopoietic system

abnormal diapedesis ( J:72818 )

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

abnormal cytotoxic T cell physiology ( J:72818 )

• 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		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:72818

Genotype
MGI:3622412

hm13

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: NOD.129S7-Ifng^tm1Ts

immune system

abnormal susceptibility to autoimmune disorder ( J:33427 )

• 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

decreased susceptibility to autoimmune diabetes ( J:95105 )

• 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

Genotype
MGI:3623448

hm14

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: NOD.Cg-Ifng^tm1Ts Prkdc^scid

immune system

decreased susceptibility to autoimmune diabetes ( J:72818 )

• 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		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:72818

Genotype
MGI:5514242

cn15

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * NOD * SJL

mortality/aging

mortality/aging ( J:196160 )

N • improved survival

immune system

immune system phenotype ( J:196160 )

N • do not develop diabetes

Genotype
MGI:5448156

cn16

• Allelic Composition: Foxo1^tm1Flv/Foxo1^tm1Flv; Ifng^tm1Ts/Ifng^tm1Ts; Foxp3^{tm4(YFP/icre)Ayr}/Foxp3⁺
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129S7/SvEvBrd * 129X1/SvJ

mortality/aging

mortality/aging ( J:189962 )

N • the lethal inflammatory phenotype is partially rescued

immune system

immune system phenotype ( J:189962 )

N • regulatory T cells are able to suppress development of colitis in Rag1 null mice receiving naive T cells

increased CD4-positive, alpha-beta T cell number ( J:189962 )

• elevated numbers in the spleen and peripheral lymph nodes are partially rescued compared to in Foxo1^tm1Flv/Foxo1^tm1Flv Foxp3^{tm4(YFP/cre)Ayr}/Foxp3⁺ mice

increased CD8-positive, alpha-beta T cell number ( J:189962 )

• elevated numbers in the spleen and peripheral lymph nodes are partially rescued compared to in Foxo1^tm1Flv/Foxo1^tm1Flv Foxp3^{tm4(YFP/cre)Ayr}/Foxp3⁺ mice

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:189962 )

• elevated numbers in the spleen and peripheral lymph nodes are partially rescued compared to in Foxo1^tm1Flv/Foxo1^tm1Flv Foxp3^{tm4(YFP/cre)Ayr}/Foxp3⁺ mice

increased CD8-positive, alpha-beta T cell number ( J:189962 )

• elevated numbers in the spleen and peripheral lymph nodes are partially rescued compared to in Foxo1^tm1Flv/Foxo1^tm1Flv Foxp3^{tm4(YFP/cre)Ayr}/Foxp3⁺ mice

Genotype
MGI:4938323

cx17

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: B6.129-Apoe^tm1Unc Ifng^tm1Ts

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:166204 )

• 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

dilated aorta ( J:166204 )

• increase in the suprarenal aortic diameter in mice infused with 500 ng/kg/min angiotensin-II compared to mutant mice wild-type for Ifng

increased susceptibility to induced aneurysm formation ( J:166204 )

• 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

growth/size/body

increased body weight ( J:166204 )

• compared to mutant mice wild-type for Ifng

Genotype
MGI:4867042

cx18

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Ldlr^tm1Her/Ldlr^tm1Her
• Genetic Background: B6.129S7-Ldlr^tm1Her Ifng^tm1Ts

cardiovascular system

atherosclerotic lesions ( J:103072 )

• after 8 or 20 weeks on a cholesterol diet aortic lesion size is reduced compared to mice homozygous for Ldlr^tm1Her alone

hematopoietic system

increased T cell number ( J:103072 )

• increase in the proportion of T cells in the blood relative to controls homozygous for Ldlr^tm1Her alone

immune system

increased T cell number ( J:103072 )

• increase in the proportion of T cells in the blood relative to controls homozygous for Ldlr^tm1Her alone

Genotype
MGI:5431918

cx19

• Allelic Composition: Csf2^tm1Mlg/Csf2^tm1Mlg; Ifng^tm1Ts/Ifng^tm1Ts; Il3^tm1Glli/Il3^tm1Glli
• Genetic Background: B6.129S-Csf2^tm1Mlg Il3^tm1Glli Ifng^tm1TsIfng^tm1Ts

endocrine/exocrine glands

increased pituitary adenoma incidence ( J:145518 )

• islet adenomas

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:145518 )

N • significantly reduced fasting blood sugar, to levels similar to controls

N • improved glucose tolerance

neoplasm

increased pituitary adenoma incidence ( J:145518 )

• islet adenomas

nervous system

increased pituitary adenoma incidence ( J:145518 )

• islet adenomas

Genotype
MGI:3721950

cx20

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: C.129-Ifng^tm1Ts Tgfb1^tm1Doe

mortality/aging

premature death ( J:69346 )

• mice survive average of 32.9 days (range 23-66 days)

growth/size/body

decreased body weight ( J:69346 )

• mice are smaller than littermate controls

cachexia ( J:69346 )

liver/biliary system

liver/biliary system phenotype ( J:69346 )

N • outwardly, livers show no visible abnormalities

liver inflammation ( J:69346 )

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

immune system

liver inflammation ( J:69346 )

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

homeostasis/metabolism

increased circulating alanine transaminase level ( J:69346 )

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

Genotype
MGI:4867045

cx21

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Prf1^tm1Sdz/Prf1^tm1Sdz
• Genetic Background: C.Cg-Prf1^tm1Sdz Ifng^tm1Ts

mortality/aging

premature death ( J:77491 )

neoplasm

abnormal tumor morphology ( J:77491 )

• some lymphomas have an unusual histiocytic appearance with a pale eosinophilic cytoplasm

increased lymphoma incidence ( J:77491 )

• incidence is increased and onset is earlier compared to mice homozygous for Prf1^tm1Sdz alone

increased B cell derived lymphoma incidence ( J:77491 )

decreased tumor latency ( J:77491 )

• incidence is increased and onset is earlier compared to mice homozygous for Prf1^tm1Sdz alone

Genotype
MGI:6452102

cx22

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Pld4^tm1.2Nemz/Pld4^tm1.2Nemz
• Genetic Background: involves: 129 * 129S7/SvEvBrd * C57BL/6J * FVB/N

hematopoietic system

hematopoietic system phenotype ( J:281205 )

N • no elevation of expression of major histocompatibility complex (MHC) class II peptides on surface of resident peritoneal macrophages

decreased NK T cell number ( J:281205 )

immune system

decreased NK T cell number ( J:281205 )

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:281205 )

• sensitive to experimental autoimmune encephalomyelitis

Genotype
MGI:4843969

cx23

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Tnfrsf1a^tm1Blt/Tnfrsf1a^tm1Blt; Tnfrsf1b^tm1Mwm/Tnfrsf1b^tm1Mwm
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

immune system

increased leukocyte cell number ( J:119206 )

• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls

increased eosinophil cell number ( J:119206 )

• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls

increased lymphocyte cell number ( J:119206 )

• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls

absent spleen germinal center ( J:119206 )

• despite the absence of germinal centers the white pulp has distinct T and B cell areas

small Peyer's patches ( J:119206 )

• grossly unidentifiable and histologically hypoplastic

abnormal lymph node cortex morphology ( J:119206 )

• thin and lack primary and secondary cortical follicles

abnormal lymph node primary follicle morphology ( J:119206 )

• absent

abnormal lymph node secondary follicle morphology ( J:119206 )

• absent

absent lymph node germinal center ( J:119206 )

lung inflammation ( J:119206 )

• develop severe inflammation 4 weeks after infection with Pneumocystis carinii

increased susceptibility to fungal infection ( J:119206 )

• 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

increased leukocyte cell number ( J:119206 )

• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls

increased eosinophil cell number ( J:119206 )

• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls

increased lymphocyte cell number ( J:119206 )

• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls

absent spleen germinal center ( J:119206 )

• despite the absence of germinal centers the white pulp has distinct T and B cell areas

respiratory system

lung inflammation ( J:119206 )

• develop severe inflammation 4 weeks after infection with Pneumocystis carinii

Genotype
MGI:4430638

cx24

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Socs1^tm1Wehi/Socs1^tm1Wehi
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6

mortality/aging

mortality/aging ( J:57474 , J:70408 )

N • unlike mice homozygous for Socs1^tm1Wehi alone, double homozygous mice survive past weaning and are overtly healthy (J:57474)

N • lethality observed in Socs1^tm1Wehi homozygotes is rescued (J:70408)

reproductive system

abnormal mammary gland growth during pregnancy ( J:70408 )

♀ • from day 16 of pregnancy, mice exhibit a higher density of lobuloalveolar units compared with wild-type mice

♀ • however, proliferation of mammary epithelium is normal

endocrine/exocrine glands

enlarged thymus medulla ( J:57474 )

• 8 of 12 mice have enlarged medulla

• however, unlike mice homozygous for Socs1^tm1Wehi alone, the cortex is normal

abnormal mammary gland growth during pregnancy ( J:70408 )

♀ • from day 16 of pregnancy, mice exhibit a higher density of lobuloalveolar units compared with wild-type mice

♀ • however, proliferation of mammary epithelium is normal

mammary gland alveolar hyperplasia ( J:70408 )

♀ • from day 16 of pregnancy, mice exhibit a higher density of lobuloalveolar units compared with wild-type mice

♀ • however, lobuloalveolar density returns to normal by day 5 of lactation

abnormal lactation ( J:70408 )

♀ • at day 18 of pregnancy, mammary glands produce more milk than in wild-type mice

cardiovascular system

abnormal lung vasculature morphology ( J:57474 )

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

hematopoietic system

hematopoietic system phenotype ( J:57474 )

N • unlike mice homozygous for Socs1^tm1Wehi alone, no hematological abnormalities are detected at 3 weeks of age

enlarged thymus medulla ( J:57474 )

• 8 of 12 mice have enlarged medulla

• however, unlike mice homozygous for Socs1^tm1Wehi alone, the cortex is normal

immune system

enlarged thymus medulla ( J:57474 )

• 8 of 12 mice have enlarged medulla

• however, unlike mice homozygous for Socs1^tm1Wehi alone, the cortex is normal

respiratory system

abnormal lung vasculature morphology ( J:57474 )

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

integument

abnormal mammary gland growth during pregnancy ( J:70408 )

♀ • from day 16 of pregnancy, mice exhibit a higher density of lobuloalveolar units compared with wild-type mice

♀ • however, proliferation of mammary epithelium is normal

mammary gland alveolar hyperplasia ( J:70408 )

♀ • from day 16 of pregnancy, mice exhibit a higher density of lobuloalveolar units compared with wild-type mice

♀ • however, lobuloalveolar density returns to normal by day 5 of lactation

abnormal lactation ( J:70408 )

♀ • at day 18 of pregnancy, mammary glands produce more milk than in wild-type mice

Genotype
MGI:4850158

cx25

• Allelic Composition: Ifng^tm1Ts/Ifng⁺; Socs1^tm1Wehi/Socs1^tm1Wehi
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6

mortality/aging

decreased survivor rate ( J:57474 )

• 8 of 12 mice died between 2 and 12 weeks of age, the remaining 4 survived

premature death ( J:57474 )

• 8 of 12 mice died between 2 and 12 weeks of age, the remaining 4 survived

Genotype
MGI:3586344

cx26

• Allelic Composition: Csf2^tm1Dran/Csf2^tm1Dran; Ifng^tm1Ts/Ifng^tm1Ts; Il3^tm1Glli/Il3^tm1Glli
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

mortality/aging

premature death ( J:83086 )

• surviving mice became moribund with time

• most died or had to be euthanized before 14 months of age

postnatal lethality, incomplete penetrance ( J:83086 )

• about 40% of homozygotes died of pneumonia in the first few weeks of life

immune system

increased eosinophil cell number ( J:83086 )

• mild eosinophilia in mice surviving beyond the first few weeks of life

increased immunoglobulin level ( J:83086 )

increased IgE level ( J:83086 )

• serum levels increased but not significantly

increased IgG1 level ( J:83086 )

• significantly higher serum IgG1 levels

• non significant increases in serum IgG2b levels

increased inflammatory response ( J:83086 )

• acute and chronic inflammatory reactions found in many organs and tissues

neoplasm

increased B cell derived lymphoma incidence ( J:83086 )

• Lymphoproliferative disease in a high proportion of mice

• develops into B cell lymphomas

increased carcinoma incidence ( J:83086 )

• solid tumors are benign to metastasizing carcinomas

increased ovarian carcinoma incidence ( J:83086 )

♀ • particularly prevalent

hematopoietic system

increased eosinophil cell number ( J:83086 )

• mild eosinophilia in mice surviving beyond the first few weeks of life

increased immunoglobulin level ( J:83086 )

increased IgE level ( J:83086 )

• serum levels increased but not significantly

increased IgG1 level ( J:83086 )

• significantly higher serum IgG1 levels

• non significant increases in serum IgG2b levels

endocrine/exocrine glands

increased ovarian carcinoma incidence ( J:83086 )

♀ • particularly prevalent

reproductive system

increased ovarian carcinoma incidence ( J:83086 )

♀ • particularly prevalent

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	systemic lupus erythematosus	DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:83086

Genotype
MGI:3783715

cx27

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Socs1^tm1Jni/Socs1^tm1Jni
• Genetic Background: involves: 129S7/SvEvBrd

immune system

increased interleukin-17 secretion ( J:132905 )

• following culturing of IL-17 producing T cells in vitro, IL-17 production is twice as high as in similarly treated wild-type cells

Genotype
MGI:5474288

cx28

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Nlrp1a^Neut1/Nlrp1a^Neut1
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

immune system

immune system phenotype ( J:191055 )

N • normal blood neutrophils and survival

brain inflammation ( J:191055 )

• develop encephalitis

nervous system

brain inflammation ( J:191055 )

• develop encephalitis

Genotype
MGI:5688500

cx29

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Tg(SFTPC-Il18)AThos/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6N * DBA/2

immune system

lung inflammation ( J:147547 )

• mice exhibit more severe emphysematous changes and pulmonary inflammation with swelled alveolar macrophages than in single transgenic mice

respiratory system

lung inflammation ( J:147547 )

• mice exhibit more severe emphysematous changes and pulmonary inflammation with swelled alveolar macrophages than in single transgenic mice

abnormal pulmonary alveolus morphology ( J:147547 )

• the mean alveolar chord length is greater than in wild-type mice and single Tg(SFTPC-Il18)AThos transgenic mice

emphysema ( J:147547 )

• mice exhibit more severe emphysematous changes and pulmonary inflammation with swelled alveolar macrophages than in single transgenic mice

abnormal lung volume ( J:147547 )

• lung volume is higher than in wild-type or single transgenic mice

Genotype
MGI:4839049

cx30

• Allelic Composition: Fas^lpr/Fas^lpr; Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: involves: 129S7/SvEvBrd * DBA/1 * MRL/Mp

immune system

decreased double-negative T cell number ( J:39600 )

• decrease in the number of CD4-CD8-B220+ alpha beta T cells compared to mice homozygous for Fas^lpr and wild-type for Ifng

abnormal spleen size ( J:39600 )

• lympadenopathy (based on spleen weight and cellularity) is reduced compared to mice homozygous for Fas^lpr and wild-type for Ifng

enlarged spleen ( J:39600 )

• at 7-8 months of age a modest increase in spleen size and cellularity is seen relative to wild-type controls

decreased immunoglobulin level ( J:39600 )

decreased IgA level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgG2a level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgG2b level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgM level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

abnormal lymph node size ( J:39600 )

• lympadenopathy (based on lymph node weight and cellularity) is reduced compared to mice homozygous for Fas^lpr and wild-type for Ifng

• in young animals lymph node size is similar to wild-type controls

enlarged lymph nodes ( J:39600 )

• at 7-8 months of age a modest increase in lymph node size and cellularity is seen relative to wild-type controls

decreased susceptibility to systemic lupus erythematosus ( J:39600 )

• while mice develop the typical autoimmune lesions, end organ disease is decreased compared to mice homozygous for Fas^lpr and wild-type for Ifng

decreased autoantibody level ( J:39600 )

• lower titers of anti-snRNP and anti-rheumatoid factors antibodies relative to mice homozygous for Fas^lpr and wild-type for Ifng at 3 and 7-8 months of age

decreased anti-nuclear antigen antibody level ( J:39600 )

• at 3 and 7-8 months of age

decreased anti-double stranded DNA antibody level ( J:39600 )

• at 3 and 7-8 months of age

homeostasis/metabolism

decreased circulating creatinine level ( J:39600 )

• levels are lower compared to mice homozygous for Fas^lpr and wild-type for Ifng

hematopoietic system

decreased double-negative T cell number ( J:39600 )

• decrease in the number of CD4-CD8-B220+ alpha beta T cells compared to mice homozygous for Fas^lpr and wild-type for Ifng

abnormal spleen size ( J:39600 )

• lympadenopathy (based on spleen weight and cellularity) is reduced compared to mice homozygous for Fas^lpr and wild-type for Ifng

enlarged spleen ( J:39600 )

• at 7-8 months of age a modest increase in spleen size and cellularity is seen relative to wild-type controls

decreased immunoglobulin level ( J:39600 )

decreased IgA level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgG2a level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgG2b level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgM level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

growth/size/body

enlarged spleen ( J:39600 )

• at 7-8 months of age a modest increase in spleen size and cellularity is seen relative to wild-type controls

Genotype
MGI:3629594

cx31

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Tnf^tm2Gkl/Tnf⁺
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6J

immune system

small intestinal inflammation ( J:108572 )

• development and severity of IBD are similar to Tnf^tm2Gkl/+, wild-type Ifng controls

digestive/alimentary system

small intestinal inflammation ( J:108572 )

• development and severity of IBD are similar to Tnf^tm2Gkl/+, wild-type Ifng controls

Genotype
MGI:3801418

cx32

• Allelic Composition: Fas^lpr/Fas^lpr; Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: MRL.Cg-Ifng^tm1Ts Fas^lpr

immune system

immune system phenotype ( J:123834 )

N • at 4 months, kidney-infiltrating macrophages are not present; deposits of glomerular immune complexes (ICs) are not observed

N • 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

N • 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

N • 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, Fas^lpr homozygotes; glomerular autoantibody deposits are not observed

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr 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 Fas^lpr homozygotes

kidney inflammation ( J:123834 )

• 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

lung inflammation ( J:123834 )

• 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

kidney inflammation ( J:123834 )

• 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

abnormal renal glomerulus morphology ( J:123834 )

• 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

lung inflammation ( J:123834 )

• 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

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr 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 Fas^lpr homozygotes

hematopoietic system

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr 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 Fas^lpr homozygotes

Genotype
MGI:3801419

cx33

• Allelic Composition: Fas^lpr/Fas^lpr; Ifng^tm1Ts/Ifng⁺
• Genetic Background: MRL.Cg-Ifng^tm1Ts Fas^lpr

mortality/aging

premature death ( J:123834 )

• 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

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr homozygotes

increased autoantibody level ( J:123834 )

• mice develop glomerular autoantibody deposits, but do not develop glomerulonephritis

glomerulonephritis ( J:123834 )

• mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months develop diffuse proliferative glomerulonephritis by 6 months

renal/urinary system

abnormal renal glomerulus morphology ( J:123834 )

• 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

abnormal glomerular capillary morphology ( J:123834 )

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

increased mesangial cell number ( J:123834 )

• mesangial cells are increased in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

glomerulonephritis ( J:123834 )

• mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months develop diffuse proliferative glomerulonephritis by 6 months

homeostasis/metabolism

increased blood urea nitrogen level ( J:123834 )

• 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

abnormal glomerular capillary morphology ( J:123834 )

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

cellular

increased mesangial cell number ( J:123834 )

• mesangial cells are increased in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr homozygotes

hematopoietic system

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr homozygotes