All Phenotypes Il6<tm1Kopf> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Il6^tm1Kopf
targeted mutation 1, Manfred Kopf
MGI:1857197

Summary

27 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Il6^tm1Kopf/Il6^tm1Kopf	B6.129S2-Il6^tm1Kopf/J	MGI:3629043
hm2	Il6^tm1Kopf/Il6^tm1Kopf	C.129S2(B6)-Il6^tm1Kopf	MGI:7764754
hm3	Il6^tm1Kopf/Il6^tm1Kopf	involves: 129S2/SvPas	MGI:3837132
hm4	Il6^tm1Kopf/Il6^tm1Kopf	involves: 129S2/SvPas * C57BL/6	MGI:2180049
hm5	Il6^tm1Kopf/Il6^tm1Kopf	involves: 129S2/SvPas * C57BL/6J * CE/J	MGI:4453191
cn6	Il6^tm1Kopf/Il6⁺ Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Itgax-cre)1-1Reiz/0	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * CBA	MGI:5515639
cn7	Il6^tm1Kopf/Il6^tm1Kopf Junb^tm3Wag/Junb^tm3Wag Tg(KRT5-cre)1Tak/0	involves: 129/Sv * 129P2/OlaHsd * 129S2/SvPas * C3H * C57BL/6	MGI:4417905
cx8	Ash1l^{Tn(pb-Act-RFP)1.AF0-180T25Zhu}/Ash1l^{Tn(pb-Act-RFP)1.AF0-180T25Zhu} Il6^tm1Kopf/Il6^tm1Kopf	B6.Cg-Ash1l^{Tn(pb-Act-RFP)1.AF0-180T25Zhu} Il6^tm1Kopf	MGI:5563040
cx9	Il6^tm1Kopf/Il6^tm1Kopf Tg(ED-L2-IL1RN/IL1B)#Tcw/?	B6.Cg-Il6^tm1Kopf Tg(ED-L2-IL1RN/IL1B)#Tcw	MGI:5308014
cx10	Il6^tm1Kopf/Il6⁺ Tg(ED-L2-IL1RN/IL1B)#Tcw/?	B6.Cg-Il6^tm1Kopf Tg(ED-L2-IL1RN/IL1B)#Tcw	MGI:5308015
cx11	Il6^tm1Kopf/Il6⁺ Ncoa5^tm1Hxia/Ncoa5⁺	involves: 129 * 129S2/SvPas * C57BL/6	MGI:7294376
cx12	Il6^tm1Kopf/Il6^tm1Kopf Inpp5d^tm1Rkh/Inpp5d^tm1Rkh	involves: 129 * C57BL/6	MGI:3838993
cx13	Il6^tm1Kopf/Il6^tm1Kopf Il6st^tm1Ern/Il6st^tm1Ern	involves: 129S1/Sv * 129S2/SvPas	MGI:3837308
cx14	Il6^tm1Kopf/Il6^tm1Kopf Lif^tm1Stw/Lif^tm1Stw	involves: 129S1/Sv * 129S2/SvPas * C57BL/6	MGI:4834760
cx15	Ctsc^tm1Ley/Ctsc^tm1Ley Il6^tm1Kopf/Il6^tm1Kopf	involves: 129S2/SvPas * 129X1/SvJ * C57BL/6	MGI:3696456
cx16	Il6^tm1Kopf/Il6⁺ Ncoa5^tm1Hxia/Ncoa5⁺	involves: 129S2/SvPas * BALB/c * C57BL/6	MGI:5581716
cx17	Il6^tm1Kopf/Il6^tm1Kopf Npc1^m1N/Npc1^m1N	involves: 129S2/SvPas * BALB/c * C57BL/6	MGI:3706955
cx18	Il6^tm1Kopf/Il6^tm1Kopf Tg(Rorc-EGFP)1Ebe/?	involves: 129S2/SvPas * C57BL/6	MGI:3829418
cx19	Foxp3^tm1Kuch/? Il6^tm1Kopf/Il6^tm1Kopf	involves: 129S2/SvPas * C57BL/6	MGI:3851995
cx20	Il6^tm1Kopf/Il6⁺ Ncoa5^tm1Hxia/Ncoa5⁺	involves: 129S2/SvPas * C57BL/6	MGI:5581715
cx21	Il6^tm1Kopf/Il6⁺ Ncoa5^tm1Hxia/Ncoa5^tm1Hxia	involves: 129S2/SvPas * C57BL/6	MGI:5581717
cx22	Apc^Min/Apc⁺ Il6^tm1Kopf/Il6^tm1Kopf	involves: 129S2/SvPas * C57BL/6	MGI:4365606
cx23	Il6^tm1Kopf/Il6^tm1Kopf Il6ra^tm1.2Drew/Il6ra^tm1.2Drew	involves: 129S2/SvPas * C57BL/6 * C57BL/6N * FVB/N * SJL	MGI:4456869
cx24	Il6^tm1Kopf/Il6^tm1Kopf Tg(H2-K-IL6)2Srj/0	involves: 129S2/SvPas * C57BL/6 * DBA/2	MGI:5582604
cx25	Galc^twi/Galc^twi Il6^tm1Kopf/Il6^tm1Kopf	involves: 129S2/SvPas * C57BL/6J * CE/J	MGI:4452118
cx26	Il6^tm1Kopf/Il6^tm1Kopf Tank^tm1Aki/Tank^tm1Aki	involves: 129/Sv * 129S2/SvPas * C57BL/6	MGI:4355832
cx27	Il11ra1^tm1Wehi/Il11ra1^tm1Wehi Il6^tm1Kopf/Il6^tm1Kopf	involves: 129/Sv * C57BL/6	MGI:3604406

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	B6.129S2-Il6^tm1Kopf/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

immune system

decreased pro-B cell number ( J:117320 )

• the percentage of CD19⁺ B cell progenitors in the bone marrow is decreased from 58% to 35%

decreased interferon-gamma secretion ( J:123351 )

• after restimulation of spleen cells with keyhole limpet hemocyanin one week following immunization of mutant mice, reduced interferon gamma production is observed

increased interleukin-4 secretion ( J:123351 )

• after restimulation of spleen cells with keyhole limpet hemocyanin one week following immunization of mutant mice, enhanced Il-4 secretion is observed

abnormal interleukin-6 secretion ( J:109359 )

• intraperitoneal administration of LPS does not induce production of Il6 in the livers of mutants compared to wild-type where expression is increase

decreased susceptibility to induced arthritis ( J:208213 )

• mice treated with collagen II exhibit a lack of disease incident with normal joints compared with wild-type mice

homeostasis/metabolism

increased body temperature ( J:105279 , J:136166 )

• injection of Il1beta results in body temperature elevation by about 0.5C (J:136166)

abnormal glucose homeostasis ( J:109359 )

• inhibition of hepatic glucose production by ICV infusion of insulin is attenuated

• inhibition of hepatic glucose production assessed by a euglycemic hyperinsulinemic clamp is also attenuated

decreased glucagon secretion ( J:139138 )

• decreased fasting glucagon levels on a high fat diet

decreased insulin secretion ( J:139138 )

• decreased fasting insulin levels on a high fat diet

impaired glucose tolerance ( J:139138 )

• impaired glucose tolerance on a high fat diet

hematopoietic system

decreased pro-B cell number ( J:117320 )

• the percentage of CD19⁺ B cell progenitors in the bone marrow is decreased from 58% to 35%

behavior/neurological

abnormal emotion/affect behavior ( J:146951 )

behavioral despair ( J:146951 )

• increased latency to "give up" in a forced swim test

increased anxiety-related response ( J:96218 , J:146951 )

• significantly decreased time spent in the open arms of an elevated maze (J:96218)

• significantly decreased number of entries into the open arms of an elevated maze (J:96218)

• less time spent in the illuminated areas of a light-dark box (J:146951)

increased fear-related response ( J:146951 )

• lower latency to escape adverse stimuli

• fewer failures to escape adverse stimuli

increased locomotor activity ( J:96218 )

• increased locomotor activity in open field tests

abnormal sleep pattern ( J:105279 , J:136166 )

• increased time in non-REM sleep after sleep deprivation persists longer than for controls but increase in time is equivalent (J:105279)

• injection of Il1beta results in reduced dark phase wakefulness (J:136166)

• injection of Il1beta results in increased non REM sleep (J:136166)

abnormal frequency of paradoxical sleep ( J:105279 )

• 30% increased time in REM sleep over a 24 hour period

• most extra REM sleep occurs in the light cycle

• length of REM bouts is normal but number of bouts increases

endocrine/exocrine glands

abnormal pancreatic alpha cell mass ( J:139138 )

• alpha cell mass fails to increase on a high fat diet as it does in controls

decreased glucagon secretion ( J:139138 )

• decreased fasting glucagon levels on a high fat diet

decreased insulin secretion ( J:139138 )

• decreased fasting insulin levels on a high fat diet

skeleton

decreased susceptibility to induced arthritis ( J:208213 )

• mice treated with collagen II exhibit a lack of disease incident with normal joints compared with wild-type mice

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	C.129S2(B6)-Il6^tm1Kopf

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

neoplasm

increased tumor incidence following infection ( J:329456 )

• nearly 80% of specific-pathogen free (SPF) mutant mice infected with Rauscher-like murine leukemia virus (RL-MuLV) exhibit leukemia by 150 days compared to 50% of SPF wild-type mice

• however, development of leukemia after infection with RL-MuLV occurs at the same latency and with similar incidence as in wild-type mice

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	involves: 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:161073 )

• 60% mortality at day 12 after inoculation with C. rodentium

immune system

abnormal T cell physiology ( J:159479 )

• mice challenged with Staphylococcus epidermidis cell-free supernatant exhibit impaired T cells (including CD4+, Th1, and Th17 cells) recruitment and production of IL17a compared with similarly treated wild-type mice

decreased interleukin-17 secretion ( J:159479 )

• mice challenged with Staphylococcus epidermidis cell-free supernatant exhibit fewer IL17a producing cells compared to in similarly treated wild-type mice

abnormal inflammatory response ( J:160966 )

• following carrageenan induced inflammation, mice exhibit impaired neutrophil resolution after 7 days and delayed macrophage infiltration compared to in similarly treated wild-type mice

increased susceptibility to bacterial infection induced morbidity/mortality ( J:161073 )

• 60% mortality at day 12 after inoculation with C. rodentium

homeostasis/metabolism

delayed wound healing ( J:160966 )

• at healing wounds, mice exhibit delayed re-epithelialization, formation of granulation tissue, macrophage infiltration, fibrin clearance, and vascularization compared with wild-type mice

impaired wound healing ( J:160966 )

• wounds become expanded beyond the boundaries of the original wound unlike in wild-type mice

decreased susceptibility to injury ( J:89814 , J:145306 )

• 24 hours after scalpel cortex injury, mice exhibit reduced microglial and astrocyte reaction compared with similarly treated wild-type mice (J:89814)

• following exposure to acid-induced acute lung injury, mice exhibit alleviated symptoms compared to wild-type mice (J:145306)

liver/biliary system

abnormal oval cell physiology ( J:66448 )

• modestly reduced oval cell response to a choline deficient diet and ethionine in the drinking water

nervous system

abnormal glial cell morphology ( J:89814 )

• 24 hours after scalpel cortex injury, mice exhibit reduced microglial and astrocyte reaction compared with similarly treated wild-type mice

hematopoietic system

abnormal T cell physiology ( J:159479 )

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

growth/size/body

decreased body weight ( J:105633 )

• lower body weight at 4 months of age is due largely to lower fat mass

obese ( J:105633 )

• obesity develops by 8 months of age

immune system

increased susceptibility to induced colitis ( J:79073 )

• severe erosion of the intestinal epithelium from exposure to 3.5% dextran sodium sulfate

abnormal T cell differentiation ( J:17360 )

• thymocytes are consistently reduced by 20-40%

decreased T cell number ( J:17360 )

• T cells are reduced in the periphery by 20-40%

abnormal microglial cell morphology ( J:79142 )

• modest increase in microglial density after haloperidol treatment relative to the increase seen in controls

decreased cytotoxic T cell cytolysis ( J:17360 )

• cytolytic activity of CD8 T cells to vaccinia virus infected cells is reduced 3-10 fold

abnormal acute phase protein level ( J:17360 )

• 100-fold reduction in SAA production by the liver in response to turpentine injection or listeria infection

increased susceptibility to bacterial infection ( J:17360 )

• 10 to 100 fold increase in bacterial titers in the liver and spleen of mice infected with Listeria

increased susceptibility to Poxviridae infection ( J:17360 )

• viral titers are 10-1000 fold higher in the ovaries and lungs of vaccinia virus infected mice

hematopoietic system

abnormal T cell differentiation ( J:17360 )

• thymocytes are consistently reduced by 20-40%

decreased T cell number ( J:17360 )

• T cells are reduced in the periphery by 20-40%

abnormal microglial cell morphology ( J:79142 )

• modest increase in microglial density after haloperidol treatment relative to the increase seen in controls

decreased cytotoxic T cell cytolysis ( J:17360 )

• cytolytic activity of CD8 T cells to vaccinia virus infected cells is reduced 3-10 fold

cardiovascular system

abnormal capillary morphology ( J:150895 )

• fewer capillaries in the heart

abnormal heart morphology ( J:150895 )

abnormal heart development ( J:150895 )

• loss of cell-cell interaction between myocytes and fibroblasts

• increased number of fibroblasts and decreased numbers of myocytes

decreased heart weight ( J:150895 )

• heart weight/body weight and heart weight/tibia length ratios both significantly reduced

abnormal heart ventricle morphology ( J:150895 )

• increased interstitial collagen in the free walls of both left and right ventricles

abnormal interventricular septum morphology ( J:150895 )

• modestly increased interstitial collagen

decreased heart left ventricle wall thickness ( J:150895 )

• both anterior and posterior walls of the left ventricle are thin

decreased heart left ventricle anterior wall thickness ( J:150895 )

decreased heart left ventricle posterior wall thickness ( J:150895 )

dilated heart left ventricle ( J:150895 )

abnormal cardiovascular system physiology ( J:150895 )

• increased cell proliferation and apoptosis in 5 day old hearts

• proliferation at 5 days primarily by non myocytes

• apoptosis at 5 days primarily of myocytes

decreased cardiac muscle contractility ( J:150895 )

• both fractional shortening and ejection fraction are decreased in adults and at 5 and 15 days of age

• cardiac dysfunction beginning at 15 days of age

• cardiac dilation is more or less normal at 5 days of age

behavior/neurological

abnormal learning/memory/conditioning ( J:147420 )

abnormal inhibitory learning ( J:147420 )

• slower to relocate platform after it is moved in a Morris water maze

abnormal object recognition memory ( J:147420 , J:148881 )

• reduced exploration in initial phase of novel object recognition tests (J:147420)

• increased exploration in novel object recognition tests (J:148881)

abnormal long-term object recognition memory ( J:148881 )

• greater object recognition memory

impaired long-term object recognition memory ( J:147420 )

• reduced object recognition when retested

abnormal spatial learning ( J:147420 )

• longer escape latencies in a Morris water maze

• shorter time spent in the target quadrant of a Morris water maze

abnormal emotion/affect behavior ( J:147420 )

behavioral despair ( J:147420 )

• increased latency to float in a forced swimming test

• reduced despair behavior

increased anxiety-related response ( J:147420 )

• more time in the closed arms of an elevated + maze after forced swimming tests

nervous system

abnormal CNS glial cell morphology ( J:79142 )

abnormal microglial cell morphology ( J:79142 )

• modest increase in microglial density after haloperidol treatment relative to the increase seen in controls

abnormal astrocyte morphology ( J:79142 )

• density fails to increase in response to neurotoxin (6-OHDA) lesioning

abnormal neuron morphology ( J:79142 )

abnormal brain interneuron morphology ( J:148881 )

• parvalbumin positive interneurons in the hippocampus suffer less loss in numbers with age

abnormal axon morphology ( J:79142 )

• axon terminal tree is 25% larger in the substantia nigra pars compacta than for controls

• resistant to the effects of haloperidol treatment on terminal trees

• neurotoxin lesion results in reduced terminal tree density

abnormal nervous system physiology ( J:148881 )

abnormal neuron physiology ( J:148881 )

• age induced increase in oxygen consumption in synaptosomes is attenuated

muscle

decreased cardiac muscle contractility ( J:150895 )

• both fractional shortening and ejection fraction are decreased in adults and at 5 and 15 days of age

• cardiac dysfunction beginning at 15 days of age

• cardiac dilation is more or less normal at 5 days of age

abnormal myoblast migration ( J:131016 )

• migration of primary myoblasts is reduced relative to controls

abnormal skeletal muscle satellite cell proliferation ( J:131016 )

• proliferation is defective

abnormal skeletal muscle fiber morphology ( J:131016 )

• cross-sectional area of myofibers does not increase after overload of the plantaris muscle by incapacitation of the gastrocnemius, measured 14 and 42 days after overload

• no change in myonuclear numbers

vision/eye

retina outer nuclear layer degeneration ( J:136895 )

• higher level of apoptosis after retinal separation from the retinal pigment epithelium

• higher rate of photoreceptor cell death after 1 month

skeleton

abnormal bone healing ( J:141482 )

• callus formed after bone fracture is denser after 2 weeks than is true in controls

• tissue mineral density is less at 4 and 6 weeks after injury than for controls

• greater collagen content at 2 weeks after fracture but not at 4 or 6 weeks

decreased bone mineral density ( J:141482 )

• mineral density of cortical bone reduced

• reduced crystallinity relative to controls

• reduced mineral/matrix ratio in cortical bone at both 2 and 4 weeks

neoplasm

decreased incidence of tumors by chemical induction ( J:122816 )

• reduced incidence of hepatocellular cancer in males treated with diethyl nitrosamine relative to incidence in control males

liver/biliary system

hepatic necrosis ( J:122816 )

• less necrosis resulting from diethyl nitrosamine treatment

liver degeneration ( J:122816 )

• less hepatic injury in males from treatment with diethyl nitrosamine

• less apoptosis due to diethyl nitrosamine treatment

• less compensatory proliferation as a result of diethyl nitrosamine treatment

respiratory system

abnormal pulmonary gas exchange ( J:105633 )

• elevated respiratory exchange rate in young mice

homeostasis/metabolism

abnormal homeostasis ( J:105633 )

increased circulating glucose level ( J:105633 )

• elevated basal glucose levels at 8 months but not in younger mice

• glucose levels do not differ from controls in young mice after 1 hour of exercise

abnormal oxygen consumption ( J:105633 )

• oxygen consumption is not maintained at as high a level after 12 minutes of running as in controls

abnormal acute phase protein level ( J:17360 )

• 100-fold reduction in SAA production by the liver in response to turpentine injection or listeria infection

abnormal exercise endurance ( J:105633 )

• reduced treadmill endurance

decreased incidence of tumors by chemical induction ( J:122816 )

• reduced incidence of hepatocellular cancer in males treated with diethyl nitrosamine relative to incidence in control males

abnormal bone healing ( J:141482 )

• callus formed after bone fracture is denser after 2 weeks than is true in controls

• tissue mineral density is less at 4 and 6 weeks after injury than for controls

• greater collagen content at 2 weeks after fracture but not at 4 or 6 weeks

endocrine/exocrine glands

abnormal involution of the mammary gland ( J:125449 )

• develops more slowly

digestive/alimentary system

increased susceptibility to induced colitis ( J:79073 )

• severe erosion of the intestinal epithelium from exposure to 3.5% dextran sodium sulfate

integument

abnormal involution of the mammary gland ( J:125449 )

• develops more slowly

cellular

abnormal myoblast migration ( J:131016 )

• migration of primary myoblasts is reduced relative to controls

abnormal skeletal muscle satellite cell proliferation ( J:131016 )

• proliferation is defective

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	involves: 129S2/SvPas * C57BL/6J * CE/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

behavior/neurological

seizures ( J:63197 )

• a substantial proportion of homozygotes develop generalized seizures after 250 days of age

nervous system

seizures ( J:63197 )

• a substantial proportion of homozygotes develop generalized seizures after 250 days of age

Allelic Composition	Il6^tm1Kopf/Il6⁺ Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Itgax-cre)1-1Reiz/0
Genetic Background	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * CBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Prdm1^tm1Clme mutation (1 available); any Prdm1 mutation (66 available)
Tg(Itgax-cre)1-1Reiz mutation (4 available)

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

immune system

immune system phenotype ( J:178876 )

• mice do not develop autoantibodies, they mount an antibody response indistinguishable from control mice to NP-CGG, dendritic cells express the same level of IL-6 as dendritic cells from control mice after LPS stimulation, and show normal levels of follicular T helper cells and germinal cells in the spleen

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf Junb^tm3Wag/Junb^tm3Wag Tg(KRT5-cre)1Tak/0
Genetic Background	involves: 129/Sv * 129P2/OlaHsd * 129S2/SvPas * C3H * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Junb^tm3Wag mutation (1 available); any Junb mutation (20 available)
Tg(KRT5-cre)1Tak mutation (0 available)

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

mortality/aging

mortality/aging ( J:155575 )

N	• mice exhibit normal lifespan unlike Junb^tm3Wag/Junb^tm3Wag Tg(KRT5-cre)1Tak mice

immune system

immune system phenotype ( J:155575 )

N	• mice exhibit a rescue of the systemic lupus erythematosus associated phenotypes observed in Junb^tm3Wag/Junb^tm3Wag Tg(KRT5-cre)1Tak mice including normal lymph node architecture, plasma cell count, and antinuclear autoantibodies

skin inflammation ( J:155575 )

• mild

renal/urinary system

renal/urinary system phenotype ( J:155575 )

N	• mice exhibit a rescue of the lupus associated kidney phenotypes observed in Junb^tm3Wag/Junb^tm3Wag Tg(KRT5-cre)1Tak mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:155575 )

N	• ce exhibit normal urine albumin levels unlike in Junb^tm3Wag/Junb^tm3Wag Tg(KRT5-cre)1Tak mice

integument

integument phenotype ( J:155575 )

N	• mice exhibit a rescue of the lupus associated skin phenotypes observed in Junb^tm3Wag/Junb^tm3Wag Tg(KRT5-cre)1Tak mice

skin inflammation ( J:155575 )

• mild

hyperkeratosis ( J:155575 )

• mild

thick skin ( J:155575 )

• milder than in Junb^tm3Wag/Junb^tm3Wag Tg(KRT5-cre)1Tak mice

Allelic Composition	Ash1l^{Tn(pb-Act-RFP)1.AF0-180T25Zhu}/Ash1l^{Tn(pb-Act-RFP)1.AF0-180T25Zhu} Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	B6.Cg-Ash1l^{Tn(pb-Act-RFP)1.AF0-180T25Zhu} Il6^tm1Kopf

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ash1l^{Tn(pb-Act-RFP)1.AF0-180T25Zhu} mutation (0 available); any Ash1l mutation (138 available)
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

immune system

abnormal inflammatory response ( J:208213 )

• reduced inflammation compared with Ash1l^{Tn(pb-Act-RFP)1.AF0-180T25Zhu} homozygotes

increased susceptibility to induced arthritis ( J:208213 )

• compared with Il6^tm1Kopf homozygotes

skeleton

increased susceptibility to induced arthritis ( J:208213 )

• compared with Il6^tm1Kopf homozygotes

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf Tg(ED-L2-IL1RN/IL1B)#Tcw/?
Genetic Background	B6.Cg-Il6^tm1Kopf Tg(ED-L2-IL1RN/IL1B)#Tcw

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Tg(ED-L2-IL1RN/IL1B)#Tcw mutation (0 available)

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

digestive/alimentary system

digestive/alimentary phenotype ( J:180282 )

N	• absence of Il6 expression completely abolishes the metaplastic and dysplastic phenotypes seen in transgenic mice expressing Il6

esophageal inflammation ( J:180282 )

• minor inflammatory response

immune system

esophageal inflammation ( J:180282 )

• minor inflammatory response

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Barrett's esophagus	DOID:9206	OMIM:614266	J:180282

Allelic Composition	Il6^tm1Kopf/Il6⁺ Tg(ED-L2-IL1RN/IL1B)#Tcw/?
Genetic Background	B6.Cg-Il6^tm1Kopf Tg(ED-L2-IL1RN/IL1B)#Tcw

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Tg(ED-L2-IL1RN/IL1B)#Tcw mutation (0 available)

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

digestive/alimentary system

digestive/alimentary phenotype ( J:180282 )

N	• reduced of Il6 expression completely decreases metaplasia and abolishes dysplasia

esophageal inflammation ( J:180282 )

immune system

esophageal inflammation ( J:180282 )

Allelic Composition	Il6^tm1Kopf/Il6⁺ Ncoa5^tm1Hxia/Ncoa5⁺
Genetic Background	involves: 129 * 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Ncoa5^tm1Hxia mutation (0 available); any Ncoa5 mutation (55 available)

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

reproductive system

teratozoospermia ( J:284227 )

• SEM and TEM analyses of cauda epididymal sperm showed significantly improved sperm ultrastructure relative to single Ncoa5^tm1Hxia male heterozygotes

increased sperm motility ( J:284227 )

• at 4 months of age, the % of motile cauda epididymal sperm is significantly higher than that in single Ncoa5^tm1Hxia male heterozygotes

increased sperm progressive motility ( J:284227 )

• at 4 months of age, the % of progressively motile sperm is significantly higher than that in single Ncoa5^tm1Hxia male heterozygotes

enhanced male fertility ( J:284227 )

• when bred with double heterozygous females, 5 out of 6 double heterozygous males are able to father litters with 2 to 8 pups per litter, in contrast to single Ncoa5^tm1Hxia male heterozygotes

abnormal epididymis physiology ( J:284227 )

• at 4.5 months of age, IHC staining showed that epididymal expression of IL-6 is markedly lower than that in single Ncoa5^tm1Hxia male heterozygotes

cellular

teratozoospermia ( J:284227 )

• SEM and TEM analyses of cauda epididymal sperm showed significantly improved sperm ultrastructure relative to single Ncoa5^tm1Hxia male heterozygotes

increased sperm motility ( J:284227 )

• at 4 months of age, the % of motile cauda epididymal sperm is significantly higher than that in single Ncoa5^tm1Hxia male heterozygotes

increased sperm progressive motility ( J:284227 )

• at 4 months of age, the % of progressively motile sperm is significantly higher than that in single Ncoa5^tm1Hxia male heterozygotes

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf Inpp5d^tm1Rkh/Inpp5d^tm1Rkh
Genetic Background	involves: 129 * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Inpp5d^tm1Rkh mutation (0 available); any Inpp5d mutation (94 available)

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

immune system

abnormal lymphopoiesis ( J:117320 )

• the percentage of prolymphocyte in the bone marrow is slightly less than wild-type (35% versus 27%)

decreased pro-B cell number ( J:117320 )

• the percentage of CD19⁺ B cell progenitors in the bone marrow is decreased by almost 4-fold

abnormal myelopoiesis ( J:117320 )

• 78% of mutant bone marrow cells are Mac-1⁺ compared to 56% in wild-type

hematopoietic system

abnormal lymphopoiesis ( J:117320 )

• the percentage of prolymphocyte in the bone marrow is slightly less than wild-type (35% versus 27%)

decreased pro-B cell number ( J:117320 )

• the percentage of CD19⁺ B cell progenitors in the bone marrow is decreased by almost 4-fold

abnormal myelopoiesis ( J:117320 )

• 78% of mutant bone marrow cells are Mac-1⁺ compared to 56% in wild-type

abnormal hematopoietic stem cell morphology ( J:117320 )

• there is a 2-fold decrease in Lin^-c-Kit^loSca-1^lo population in the bone marrow that contains the hematopoietic stem cell population

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf Il6st^tm1Ern/Il6st^tm1Ern
Genetic Background	involves: 129S1/Sv * 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6st^tm1Ern mutation (13 available); any Il6st mutation (80 available)
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

immune system

immune system phenotype ( J:139226 )

N	• neutrophil infiltration of the peritoneal cavity and subsequent clearance in induced inflammation normal

decreased susceptibility to endotoxin shock ( J:168781 )

• mice are resistant to LPS-induced shock

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf Lif^tm1Stw/Lif^tm1Stw
Genetic Background	involves: 129S1/Sv * 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Lif^tm1Stw mutation (1 available); any Lif mutation (11 available)

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

homeostasis/metabolism

decreased susceptibility to injury ( J:89814 )

• 24 hours after scalpel cortex injury, mice exhibit reduced microglial and astrocyte reaction compared with similarly treated wild-type mice but similar to in single homozygotes

nervous system

abnormal glial cell morphology ( J:89814 )

• 24 hours after scalpel cortex injury, mice exhibit reduced microglial and astrocyte reaction compared with similarly treated wild-type mice but similar to in single homozygotes

Allelic Composition	Ctsc^tm1Ley/Ctsc^tm1Ley Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	involves: 129S2/SvPas * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctsc^tm1Ley mutation (0 available); any Ctsc mutation (37 available)
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

immune system

immune system phenotype ( J:88160 )

N	• survival of experimentally induced sepsis is similar to that of controls

Allelic Composition	Il6^tm1Kopf/Il6⁺ Ncoa5^tm1Hxia/Ncoa5⁺
Genetic Background	involves: 129S2/SvPas * BALB/c * C57BL/6

Find Mice

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:207622 )

N	• unlike Ncoa5^tm1Hxia male heterozygotes, male mice exhibit normal circulating glucose levels and improved glucose tolerance

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf Npc1^m1N/Npc1^m1N
Genetic Background	involves: 129S2/SvPas * BALB/c * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Npc1^m1N mutation (3 available); any Npc1 mutation (74 available)

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

nervous system

abnormal glial cell physiology ( J:118352 )

• nmber of activated microglial and astroglial cells is decreased in 6-week old mice compared to Il6-sufficient, Npc1-null mice

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf Tg(Rorc-EGFP)1Ebe/?
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Tg(Rorc-EGFP)1Ebe mutation (0 available)

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

hematopoietic system

abnormal effector T cell morphology ( J:137020 )

• splenic Th-17 cells that have alphabeta TCR and are GFP-positive are decreased by half compared to controls

• the ratio of IL-17 producing cells to IL-10 producing cells among the GFP-positive T cell population is significantly decreased

• numbers of Th17 gammadelta T cells are normal

immune system

abnormal effector T cell morphology ( J:137020 )

• splenic Th-17 cells that have alphabeta TCR and are GFP-positive are decreased by half compared to controls

• the ratio of IL-17 producing cells to IL-10 producing cells among the GFP-positive T cell population is significantly decreased

• numbers of Th17 gammadelta T cells are normal

Allelic Composition	Foxp3^tm1Kuch/? Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxp3^tm1Kuch mutation (1 available); any Foxp3 mutation (58 available)
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

hematopoietic system

abnormal CD4-positive T cell differentiation ( J:123352 )

• immunization with MOG-peptide leads to less differentiation of Th17 effector cells

• when Treg cells are depleted, Th17 T cells form upon MOG immunization

• nave T cells can be differentiated in vitro to Th17 T cells by incubating with Tgf-beta plus IL-21 albeit to a lesser degree than controls

increased regulatory T cell number ( J:123352 )

• numbers of FoxP3⁺ T cells are increased in MOG-immunized mice compared to immunized controls

• the ratio of MOG-specific Treg to effector T cells is reversed compared to controls

homeostasis/metabolism

decreased circulating interleukin-6 level ( J:123352 )

• mice were confirmed not to produce IL-6

immune system

abnormal CD4-positive T cell differentiation ( J:123352 )

• immunization with MOG-peptide leads to less differentiation of Th17 effector cells

• when Treg cells are depleted, Th17 T cells form upon MOG immunization

• nave T cells can be differentiated in vitro to Th17 T cells by incubating with Tgf-beta plus IL-21 albeit to a lesser degree than controls

increased regulatory T cell number ( J:123352 )

• numbers of FoxP3⁺ T cells are increased in MOG-immunized mice compared to immunized controls

• the ratio of MOG-specific Treg to effector T cells is reversed compared to controls

decreased circulating interleukin-6 level ( J:123352 )

• mice were confirmed not to produce IL-6

decreased interleukin-17 secretion ( J:123352 )

• less IL-17 is secreted when T cells from MOG-challenged mice are presented MOG peptide in vitro

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:123352 )

• mice are resistant to EAE induced by immunization with MOG-peptide

Allelic Composition	Il6^tm1Kopf/Il6⁺ Ncoa5^tm1Hxia/Ncoa5⁺
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

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

liver/biliary system

increased hepatocellular carcinoma incidence ( J:207622 )

• fewer and smaller maximum tumor volume than in Ncoa5^tm1Hxia male heterozygotes

reproductive system

reproductive system phenotype ( J:207622 )

N	• unlike Ncoa5^tm1Hxia male heterozygotes, male mice are fertile

neoplasm

increased hepatocellular carcinoma incidence ( J:207622 )

• fewer and smaller maximum tumor volume than in Ncoa5^tm1Hxia male heterozygotes

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:207622 )

N	• unlike Ncoa5^tm1Hxia male heterozygotes, male mice exhibit normal circulating glucose levels, glucose tolerance and insulin sensitivity

Allelic Composition	Il6^tm1Kopf/Il6⁺ Ncoa5^tm1Hxia/Ncoa5^tm1Hxia
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

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

mortality/aging

preweaning lethality, complete penetrance ( J:207622 )

• no mice are produced from fertile double heterozygotes

Allelic Composition	Apc^Min/Apc⁺ Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apc^Min mutation (12 available); any Apc mutation (158 available)
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

muscle

muscle phenotype ( J:130429 )

N	• no gastrocnemius muscle wasting

adipose tissue

adipose tissue phenotype ( J:130429 )

N	• normal epididymal fat pads

neoplasm

abnormal tumor incidence ( J:130429 )

• numbers of gastrointestinal polyps 32% lower at 26 weeks than when both Il6 alleles are wild-type

• polyp sizes are reduced

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf Il6ra^tm1.2Drew/Il6ra^tm1.2Drew
Genetic Background	involves: 129S2/SvPas * C57BL/6 * C57BL/6N * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6ra^tm1.2Drew mutation (0 available); any Il6ra mutation (35 available)
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

homeostasis/metabolism

abnormal wound healing ( J:160966 )

• mice exhibit delayed re-epithelialization of small and large wounds is delayed compared to in wild-type mice

• mice exhibit deficits in the formation of granulation tissue at wounds compared with wild-type mice

• however, macroscopic wound closure rates are normal

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf Tg(H2-K-IL6)2Srj/0
Genetic Background	involves: 129S2/SvPas * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Tg(H2-K-IL6)2Srj mutation (0 available)

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

hematopoietic system

hematopoietic system phenotype ( J:185153 )

N	• mice exhibit normal spleen and lymph node size, normal IgG levels and do not show hyperplastic germinal centers, extramedullary hematopoiesis, or plasmacytosis in lymphoid tissues at 4-5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	viral infectious disease	DOID:934		J:185153

Allelic Composition	Galc^twi/Galc^twi Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	involves: 129S2/SvPas * C57BL/6J * CE/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Galc^twi mutation (1 available); any Galc mutation (46 available)
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

behavior/neurological

tremors ( J:56656 )

• the average onset of twitching is earlier in double homozygotes than mice homozygous only for twitcher (22.2 days of age versus 25.9 days of age respectively), although lifespan, body weight and frequency of twitching do not differ significantly

nervous system

abnormal blood-brain barrier function ( J:56656 )

• leakage of the blood-brain barrier is detected in the cerebrum, hindbrain, and cervical spinal cord as detected by horseradish peroxidase tail vein injection, and immunoglobulin and albumin immunohistochemistry

• lipopolysaccharide injection greatly enhances the blood-brain barrier disruption leading to death

abnormal cerebellum white matter morphology ( J:56656 )

• the deep cerebellar white matter shows a significant increase in periodic acid-Schiff staining cells and a trend toward increased lectin-positive cells relative to mice homozygous only for twitcher

gliosis ( J:56656 )

• more exaggerated gliosis is found around some vessels and pial surfaces in the double mutants than in mice homozygous only for twitcher

cardiovascular system

abnormal blood-brain barrier function ( J:56656 )

• lipopolysaccharide injection greatly enhances the blood-brain barrier disruption leading to death

homeostasis/metabolism

abnormal tumor necrosis factor level ( J:56656 )

• hindbrain has TNF levels elevated above that found in mice homozygous only for twitcher and mice homozygous only for twitcher have significantly elevated TNF levels in hindbrain

immune system

abnormal tumor necrosis factor level ( J:56656 )

• hindbrain has TNF levels elevated above that found in mice homozygous only for twitcher and mice homozygous only for twitcher have significantly elevated TNF levels in hindbrain

Allelic Composition	Il6^tm1Kopf/Il6^tm1Kopf Tank^tm1Aki/Tank^tm1Aki
Genetic Background	involves: 129/Sv * 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)
Tank^tm1Aki mutation (0 available); any Tank mutation (30 available)

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

immune system

immune system phenotype ( J:151757 )

N	• the glomerulonephritis and the auto-antibodies that occur in Tank-null mice do not occur on a IL-6 deficient background

Allelic Composition	Il11ra1^tm1Wehi/Il11ra1^tm1Wehi Il6^tm1Kopf/Il6^tm1Kopf
Genetic Background	involves: 129/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il11ra1^tm1Wehi mutation (1 available); any Il11ra1 mutation (37 available)
Il6^tm1Kopf mutation (9 available); any Il6 mutation (38 available)

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

digestive/alimentary system

increased susceptibility to induced colitis ( J:79073 )

• adult double homozygotes do NOT develop spontaneous gastric hyperplasia or gastric adenomas

• however, double homozygotes exhibit enhanced colitis in response to DSS-mediated intestinal injury, as shown by increased inflammation, crypt damage, severe weight loss, and increased morbidity relative to wild-type or Il11ra1^tm1Wehi mice

immune system

increased susceptibility to induced colitis ( J:79073 )

• adult double homozygotes do NOT develop spontaneous gastric hyperplasia or gastric adenomas

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